European Glaucoma Prevention Study Research Articles

Retinal Nerve Fiber Layer Optical Texture Analysis: Detecting Axonal Fiber Bundle Defects in Patients with Ocular Hypertension

To apply retinal nerve fiber layer (RNFL) optical texture analysis (ROTA) to investigate the prevalence, patterns, and risk factors of RNFL defects in patients with ocular hypertension (OHT) who showed normal optic disc and RNFL configuration in clinical examination, normal RNFL thickness on OCT analysis, and normal visual field (VF) results. Cross-sectional study. Six hundred eyes of 306 patients with OHT. All participants underwent clinical examination of the optic disc and RNFL, OCT RNFL imaging, and 24-2 standard automated perimetry. To detect RNFL defects, ROTA was applied. The risk score for glaucoma development was calculated according to the Ocular Hypertension Treatment Study and European Glaucoma Prevention Study (OHTS-EGPS) risk prediction model. Risk factors associated with RNFL defects were analyzed using multilevel logistic regression analysis. Prevalence of RNFL defects. The average intraocular pressure (IOP) measured from 3 separate visits within 6 months was 24.9 ± 1.8 mmHg for the eye with higher IOP and 23.7 ± 1.7 mmHg for the eye with lower IOP; the respective central corneal thicknesses were 568.7 ± 30.8 μm and 568.8 ± 31.2 μm. Of 306 patients with OHT, 10.8% (33 patients, 37 eyes) demonstrated RNFL defects in ROTA in at least 1 eye. Of the 37 eyes with RNFL defects, the superior arcuate bundle was the most frequently involved (62.2%), followed by the superior papillomacular bundle (27.0%) and the inferior papillomacular bundle (21.6%). Papillofoveal bundle defects were observed in 10.8% of eyes. The smallest RNFL defect spanned 0.0° along Bruch's membrane opening margin, whereas the widest RNFL defect extended over 29.3°. Age (years) (odds ratio [OR], 1.08; 95% confidence interval [CI], 1.03-1.13), VF pattern standard deviation (decibels [dB]) (OR, 1.82; 95% CI, 1.01-3.29), cup volume (mm3) (OR, 1.24; 95% CI, 1.01-1.53), and the OHTS-EPGS risk score (OR, 1.04; 95% CI, 1.01-1.07) were associated with RNFL defects. A considerable proportion of patients with OHT who showed no signs of optic disc and RNFL thickness abnormalities on clinical and OCT examination exhibited RNFL defects on ROTA. Axonal fiber bundle defects on ROTA may represent the earliest discernible sign of glaucoma in the glaucoma continuum. Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Evaluation of a Primary Open-Angle Glaucoma Prediction Model Using Long-term Intraocular Pressure Variability Data

The contribution of long-term intraocular pressure (IOP) variability to the development of primary open-angle glaucoma is still controversial. To assess whether long-term IOP variability data improve a prediction model for the development of primary open-angle glaucoma (POAG) in individuals with untreated ocular hypertension. This post hoc secondary analysis of 2 randomized clinical trials included data from 709 of 819 participants in the observation group of the Ocular Hypertension Treatment Study (OHTS) followed up from February 28, 1994, to June 1, 2002, and 397 of 500 participants in the placebo group of the European Glaucoma Prevention Study (EGPS) followed up from January 1, 1997, to September 30, 2003. Data analyses were completed between January 1, 2019, and March 15, 2020. The original prediction model for the development of POAG included the following baseline factors: age, IOP, central corneal thickness, vertical cup-disc ratio, and pattern SD. This analysis tested whether substitution of baseline IOP with mean follow-up IOP, SD of IOP, maximum IOP, range of IOP, or coefficient of variation IOP would improve predictive accuracy. The C statistic was used to compare the predictive accuracy of multivariable landmark Cox proportional hazards regression models for the development of POAG. Data from the OHTS consisted of 97 POAG end points from 709 of 819 participants (416 [58.7%] women; 177 [25.0%] African American and 490 [69.1%] white; mean [SD] age, 55.7 [9.59] years; median [range] follow-up, 6.9 [0.96-8.15] years). Data from the EGPS consisted of 44 POAG end points from 397 of 500 participants in the placebo group (201 [50.1%] women; 397 [100%] white; mean [SD] age, 57.8 [9.76] years; median [range] follow-up, 4.9 [1.45-5.76] years). The C statistic for the original prediction model was 0.741. When a measure of follow-up IOP was substituted for baseline IOP in this prediction model, the C statistics were as follows: mean follow-up IOP, 0.784; maximum IOP, 0.781; SD of IOP, 0.745; range of IOP, 0.741; and coefficient of variation IOP, 0.729. The C statistics in the EGPS were similarly ordered. No measure of IOP variability, when added to the prediction model that included mean follow-up IOP, age, central corneal thickness, vertical cup-disc ratio, and pattern SD, increased the C statistic by more than 0.007 in either cohort. Evidence from the OHTS and the EGPS suggests that long-term variability does not add substantial explanatory power to the prediction model as to which individuals with untreated ocular hypertension will develop POAG.

Variability of the risk factors measurements and 5-year glaucoma risk estimation.

The risk factors of the development of primary open angle glaucoma (POAG) in patients with ocular hypertension (OHT) were identified according to the joint results of the ocular hypertension treatment study (OHTS) and the European glaucoma prevention study (EGPS): namely older age, higher intraocular pressure (IOP), thinner central corneal thickness (CCT), larger vertical cup-disc ratio (VCDR) and a greater pattern standard deviation (PSD) value of Visual field (VF) test. Base on the results, a risk calculator that predict the 5-year risk of POAG development was developed. This allows integration of all the variables into one single and quantifiable unit. It could also aid clinical decision-making. However, these risk factors change over time and are subjected to measurement variabilities. For instance, the differences in the measurement of VCDR by different persons or modalities could lead to significant variability in the 5-year risk calculation, which could also affect clinical decision. In this commentary, we summarise and discuss the latest literature on the variability of VCDR measurement, its impact on glaucoma risk calculation, the limitation of the current risk calculator and the potential future development of a risk assessment model for OHT.

Correlations Between the Individual Risk for Glaucoma and RNFL and Optic Disc Morphometrical Evaluations in Ocular Hypertensive Patients.

To assess the correlation between the 5-year risk of developing primary open-angle glaucoma (POAG) [on the basis of the Ocular Hypertension Treatment Study (OHTS)-European Glaucoma Prevention Study (EGPS) model] and optic nerve head and retinal nerve fiber layer (RNFL) indices as evaluated by optical coherence tomography (Stratus OCT), scanning laser polarimetry (GDx ECC), and confocal laser ophthalmoscopy [Heidelberg Retinal Tomograph (HRT) III] in ocular hypertensive (OHT) individuals. Sixty-eight OHT individuals with the untreated intraocular pressure in both eyes between 22 and 32 mm Hg, an ophthalmoscopically normal optic disc with a cup/disc ratio asymmetry between the 2 eyes of ≤0.2, and a visual field with glaucoma hemifield test within normal limits, and pattern SD within P<0.05 were recruited. A comprehensive glaucoma workup and examination by means of OCT, GDx ECC, and HRT III were performed in all of the patients. The probability of developing POAG in 5 years was calculated by means of the OHTS-EGPS model (risk calculator score-RS), which has been developed by the OHTS-EGPS Collaborative Study Group by taking into account the age and the mean values of the central corneal thickness, the intraocular pressure, the pattern SD, and the cup/disc ratio collected in the 2 eyes. Correlations between the individual RS and OCT, GDx, and HRT parameters were then assessed by regression analysis (exponential and linear), with a statistically significant level of P<0.01. The RS of the 68 individuals ranged between 1.5% and 28.6%, with a mean of 10.2% (SD 6.4). Only OCT RNFL-related parameters showed a statistically significant correlation with the RS. The average RNFL thickness had an exponential regression r of 0.21 (P<0.0001) and a linear regression r of 0.14 (P=0.0012); the superior average RNFL thickness had an exponential regression r of 0.26 (P<0.0001) and a linear regression r of 0.23 (P<0.0001); the nasal average RNFL thickness had an exponential regression r of only 0.12 (P=0.0031). Neither GDx RNFL-related parameters nor HRT disc-related parameters showed statistically significant correlations with the RC score. This explorative study showed that the individual risk to develop POAG within 5 years in OHT individuals is significantly correlated with OCT RNFL parameters, but not with GDx RNFL parameters or HRT disc parameters. OCT parameters could explain about 20% to 25% of the variability in individual RS. The RS seems to take into account the subclinical RNFL thinning shown by the OCT.

Clinical Impact of 8 Prospective, Randomized, Multicenter Glaucoma Trials

To determine the impact of 8 multicenter randomized clinical trials (RCTs) on glaucoma practice. An electronic survey was distributed to the members of the American Glaucoma Society (AGS). Each participant was asked 2 study-specific questions and 1 standard question common to all 8 RCTs assessing the study's impact on clinical practice. RCTs included in the survey were the Advanced Glaucoma Intervention Study (AGIS), Collaborative Initial Glaucoma Treatment Study (CIGTS), Collaborative Normal Tension Glaucoma (CNTG) Study, European Glaucoma Prevention Study (EGPS), Early Manifest Glaucoma Trial (EMGT), Glaucoma Laser Trial (GLT), Ocular Hypertension Treatment Study (OHTS), and Tube Versus Trabeculectomy (TVT) Study. A 5-point Likert scale was used for rating all responses. The practice setting and duration of glaucoma practice was determined for all AGS members who responded. A total of 206 (23.0%) of 894 AGS members participated in the survey. Among those who responded, 46.4% were self classified as academic practitioners and 53.6% worked in a private practice setting. Mean Likert scores for the standard question evaluating the overall impact of the RCT were OHTS 4.47, CNTG Study 4.13, AGIS 3.78, TVT Study 3.53, EMGT 3.48, CIGTS 3.44, GLT 3.39, and 2.69 EGPS. Substantial differences were observed in the clinical impact of several RCTs in glaucoma. The reported impact of each study likely reflects several factors including study timing, design, conduct, and interpretation of results.

Predictive Value of Heidelberg Retina Tomograph Parameters for the Development of Glaucoma in the European Glaucoma Prevention Study

To determine whether baseline Heidelberg Retina Tomograph (HRT) measurements of the optic disc are associated with the development of open-angle glaucoma (OAG) in individuals with ocular hypertension in the European Glaucoma Prevention Study (EGPS). Retrospective analysis of a prospective, randomized, multicenter, double-masked, controlled clinical trial. There were 489 participants in the HRT Ancillary Study to the EGPS. Each baseline HRT parameter was assessed in univariate and multivariate proportional hazards models to determine its association with the development of OAG. Proportional hazards models were used to identify HRT variables that predicted which participants in the EGPS had developed OAG. Development of OAG was based on visual field and/or optic disc changes. At a median follow-up time of about 5 years, 61 participants developed OAG. In multivariate analyses, adjusting for randomization arm, age, baseline IOP, central corneal thickness, pattern standard deviation, and HRT disc area, the following HRT parameters were associated with the development of OAG: the "outside normal limits" classification of the Frederick Mikelberg (FSM) discriminant function (hazard ratio [HR] 2.51, 95% confidence interval [CI]: 1.45-4.35), larger mean cup depth (HR 1.64, 95% CI: 1.21-2.23), cup-to-disc area ratio (HR 1.43, 95% CI: 1.14-1.80), linear cup-to-disc ratio (HR 1.43, 95% CI: 1.13-1.80), cup area (HR 1.33, 95% CI: 1.08-1.64), smaller rim area (HR 1.33, 95% CI: 1.07-1.64), larger cup volume (HR 1.30, 95% CI: 1.05-1.61), smaller rim volume (HR 1.25, 95% CI: 1.01-1.54), larger maximum cup depth (HR 1.18, 95% CI: 1.01-1.36), and cup shape measure (HR 1.18, 95% CI: 1.01-1.36). Several baseline HRT parameters, alone or in combination with baseline clinical and demographic factors, were significantly associated with the development of OAG among the EGPS participants.

Risk Calculation Variability Over Time in Ocular Hypertensive Subjects

To investigate the longitudinal variability of glaucoma risk calculation in ocular hypertensive (OHT) subjects. We reviewed the charts of untreated OHT patients followed in a glaucoma referral practice for a minimum of 60 months. Clinical variables collected at baseline and during follow-up included age, central corneal thickness (CCT), intraocular pressure (IOP), vertical cup-to-disc ratio (VCDR), and visual field pattern standard deviation (VFPSD). These were used to calculate the 5-year risk of conversion to primary open-angle glaucoma (POAG) at each follow-up visit using the Ocular Hypertension Treatment Study and European Glaucoma Prevention Study calculator (http://ohts.wustl.edu/risk/calculator.html). We also calculated the risk of POAG conversion based on the fluctuation of measured variables over time assuming the worst case scenarios (final age, highest PSD, lowest CCT, highest IOP, and highest VCDR) and best case scenarios (baseline age, lowest PSD, highest CCT, lowest IOP, and lowest VCDR) for each patient. Risk probabilities (%) were plotted against follow-up time to generate slopes of risk change over time. We included 27 untreated OHT patients (54 eyes) followed for a mean of 98.3±18.5 months. Seven individuals (25.9%) converted to POAG during follow-up. The mean 5-year risk of conversion for all patients in the study group ranged from 2.9% to 52.3% during follow-up. The mean slope of risk change over time was 0.37±0.81% increase/y. The mean slope for patients who reached a POAG endpoint was significantly greater than for those who did not (1.3±0.78 vs. 0.042±0.52%/y, P<0.01). In each patient, the mean risk of POAG conversion increased almost 10-fold when comparing the best case scenario with the worst case scenario (5.0% vs. 45.7%, P<0.01). The estimated 5-year risk of conversion to POAG among untreated OHT patients varies significantly during follow-up, with a trend toward increasing over time. Within the same individual, the estimated risk can vary almost 10-fold based on the variability of IOP, CCT, VCDR, and VFPSD. Therefore, a single risk calculation measurement may not be sufficient for accurate risk assessment, informed decision-making by patients, and physician treatment recommendations.

The Heidelberg retina tomograph ancillary study to the European glaucoma prevention study: study design and baseline factors

To describe the study design and baseline factors of the Heidelberg Retina Tomograph ancillary study within the EGPS. Furthermore, to examine the relationship between HRT optic disc topographic measurements and baseline demographic and ocular factors. Four hundred and eighty-nine ocular hypertensive participants were included. Each participant completed HRT imaging at least annually. The associations between HRT measurements and IOP, central corneal thickness (CCT), baseline photographic estimates of vertical CDR ratio (CDR), asymmetry between the two eyes in CDR ratio and baseline visual field indices were assessed using regression analysis. Associations between HRT measurements and vertical CDR by photographs were found for almost all stereometric optic disc parameters in both univariate and multivariate analysis. The strongest association was found between vertical CDR measurements and disc, cup and rim area; cup and rim volume, CDR area, linear CDR, mean and maximum cup depth and cup shape measure (all p < 0.0001). In multivariate analysis, pattern standard deviation (PSD) and HRT disc area had significant associations with several HRT optic disc measurements. Furthermore, CCT was significantly associated with reference height and the glaucoma probability score (GPS, outside normal limits). The EGPS is the first multicentre, placebo-controlled randomized clinical trial to use HRT for monitoring optic disc changes in participants with ocular hypertension. We found strong associations between stereophotographic vertical CDR estimates, HRT disc area, PSD and several HRT parameters. We found, furthermore, that the parameters reference height and GPS were significantly related to central corneal thickness.

The effect of changes in intraocular pressure on the risk of primary open-angle glaucoma in patients with ocular hypertension: an application of latent class analysis

BackgroundPrimary open-angle glaucoma (POAG) is one of the leading causes of blindness in the United States and worldwide. While lowering intraocular pressure (IOP) has been proven to be effective in delaying or preventing the onset of POAG in many large-scale prospective studies, one of the recent hot topics in glaucoma research is the effect of IOP fluctuation (IOP lability) on the risk of developing POAG in treated and untreated subjects.MethodIn this paper, we analyzed data from the Ocular Hypertension Treatment Study (OHTS) and the European Glaucoma Prevention Study (EGPS) for subjects who had at least 2 IOP measurements after randomization prior to POAG diagnosis. We assessed the interrelationships among the baseline covariates, the changes of post-randomization IOP over time, and the risk of developing POAG, using a latent class analysis (LCA) which allows us to identify distinct patterns (latent classes) of IOP trajectories.ResultThe IOP change in OHTS was best described by 6 latent classes differentiated primarily by the mean IOP levels during follow-up. Subjects with high post-randomization mean IOP level and/or large variability were more likely to develop POAG. Five baseline factors were found to be significantly predictive of the IOP classification in OHTS: treatment assignment, baseline IOP, gender, race, and history of hypertension. In separate analyses of EGPS, LCA identified different patterns of IOP change from those in OHTS, but confirmed that subjects with high mean level and large variability were at high risk to develop POAG.ConclusionLCA provides a useful tool to assess the impact of post-randomization IOP level and fluctuation on the risk of developing POAG in patients with ocular hypertension. The incorporation of post-randomization IOP can improve the overall predictive ability of the original model that included only baseline risk factors.

The times they are a‐changin’: time to change glaucoma management

The times they are a‐changin’: time to change glaucoma management

Argumente für eine prophylaktische Therapie der okulären Hypertension

Increased intraocular pressure is currently the only manipulable risk factor for glaucoma. In ocular hypertension the intraocular pressure is increased but the optic nerve head and visual field are thought to show no damage. Classification into glaucoma by means of the optic nerve head is often possible only over a period of time because there is a large overlap between the already pathological and still normal findings. In the Ocular Hypertension Treatment Study (OHTS) the effectiveness of prophylactic treatment was demonstrated. In the OHTS and the European Glaucoma Prevention Study (EGPS) risk factors have been identified, such as increased intraocular pressure, size of the excavation of the optic nerve head, decreased central corneal thickness, increased pattern standard deviation in the visual field and age. Before treatment of ocular hypertension is initiated these risk factors and the patient's personal situation should be considered. The higher the intraocular pressure, the smaller the central corneal thickness and the larger the excavation of the optic nerve and the younger the patient, the earlier treatment should be started.

Agreement and Accuracy of Non-Expert Ophthalmologists in Assessing Glaucomatous Changes in Serial Stereo Optic Disc Photographs

To compare the interobserver agreement in detecting glaucomatous optic disc changes using serial stereophotography between a large group of non-expert ophthalmologists and glaucoma specialists; to assess the accuracy of non-experts; to investigate whether the interobserver agreement and the accuracy of non-experts changed after a training session. Masked interobserver agreement study. Serial optic disc stereophotos from 40 patients with glaucoma. Three independent experienced glaucoma specialists (readers of the European Glaucoma Prevention Study) evaluated a set of 2 serial optic disc color stereo-slides for glaucomatous change, obtained with a delay varying from 2 to 7 years of 40 patients, masked from the temporal sequence of the slides. Each patient was graded as changed or stable by agreement of 2 of 3 of the experts (the reference standard). Thirty-seven non-expert ophthalmologists independently evaluated the same set of serial optic disc stereo-slides twice, with the second evaluation on the same day, masked from the results of the previous evaluation, after a training session on a separate slide set. Interobserver agreement of non-experts and experts in detecting glaucomatous optic disc changes (expressed as kappa coefficient); agreement of non-experts with the reference standard (accuracy) before and after a training session. The interobserver kappa coefficient (κ) of the non-experts and experts was 0.20 (95% confidence interval [CI], 0.19-0.21) and 0.51 (95% CI, 0.33-0.69), respectively (P<0.0001). The mean κ of the non-experts with the reference standard was 0.33 (95% CI, 0.27-0.39). After a training session, the interobserver agreement of the non-experts increased from 0.20 to 0.27 (95% CI, 0.26-0.28) (P<0.0001). The percentage agreement of the non-experts with the reference standard improved from 68.5% before to 71.4% after the training session (Wilcoxon signed-rank test, P=0.034). The interobserver agreement of non-expert ophthalmologists in detecting glaucomatous optic disc changes using serial stereophotos was significantly lower than that of experts, which was moderate. After a training session, the interobserver agreement and the accuracy of the non-experts showed a small but statistically significant improvement.

Quantifying the effect of intraocular pressure reduction on the occurrence of glaucoma

To estimate the effect of reducing intraocular pressure (IOP) on: (i) the incidence of primary open-angle glaucoma (POAG) in patients with ocular hypertension (OH), and (ii) the progression of glaucoma. A meta-analysis of relevant randomized controlled trials was conducted. A literature search was performed to identify trials with: a randomized comparison of IOP-lowering intervention versus placebo or no treatment; visual field loss or optic disc changes as outcome; and follow-up >6 months. A pooled relative risk (RR) was calculated by a random effects model. Risk reduction of glaucoma conversion per mmHg of IOP reduction was quantified in a meta-regression model. We identified nine OH and one POAG trials. A meta-analysis of OH trials gives a pooled RR of 0.61 [95% confidence interval (CI) 0.45-0.83]. A meta-regression shows a decrease of the RR of glaucoma conversion by 14% with each mmHg extra IOP reduction (P = 0.045). No meta-analysis of POAG trials was performed because only one study has been identified. There is sufficient evidence that OH therapy reduces the risk of conversion to glaucoma. This risk reduction increases with greater IOP reduction.

The Accuracy and Clinical Application of Predictive Models for Primary Open-Angle Glaucoma in Ocular Hypertensive Individuals

This report compares the accuracy of 3 prediction models for the development of primary open-angle glaucoma (POAG). The models differ primarily in their handling of these eye-specific variables: intraocular pressure (IOP), central corneal thickness (CCT), vertical cup-to-disc ratio (VCD), and visual field pattern standard deviation (PSD). The "means" model includes age and the means of right and left eyes; the "means plus asymmetry" model includes age, the means of right and left eyes as well as the absolute difference between eyes for eye-specific variables; and the "worse" eye model includes age and values from the eye at higher risk for developing POAG. This report uses data from the observation group of the Ocular Hypertension Treatment Study (OHTS) and the placebo group of the European Glaucoma Prevention Study (EGPS) who have complete data on both eyes at baseline. Performance of the prediction models is assessed using the c-statistic, calibration chi-square, and Pearson correlation coefficient. The OHTS observation group (n = 717; 6.7 years median follow-up) and the EGPS placebo group (n = 324; 4.9 years median follow-up). Baseline data included demographic characteristics, medical history, ocular examination, visual fields, and optic disc photographs. Development of reproducible visual field abnormality or optic disc deterioration as determined by masked readers and attributed to POAG by a masked end point committee. Baseline factors that were statistically significant in all predictive models were age, IOP, CCT, VCD, and PSD. Also, statistically significant were baseline asymmetry in IOP and asymmetry in VCD. The c-statistics for the "means" model, "means plus asymmetry" model, and "worse" eye model were 0.74, 0.77, and 0.75, respectively. The calibration chi-square values were 7.32, 11.19, and 1.81, respectively. Correlation coefficients between risk estimates calculated by different models ranged from 0.94 to 0.98. The high agreement between the risk estimates from 3 different predictive models for the development of POAG suggests little difference in their statistical or clinical performance. The predictive model that uses the means of both eyes for eye-specific variables is the simplest to use and the most robust to measurement variability and error.

Intercurrent Factors Associated with the Development of Open-Angle Glaucoma in the European Glaucoma Prevention Study

To evaluate the intercurrent factors for the development of open-angle glaucoma (OAG) in ocular hypertensive patients who were enrolled in the European Glaucoma Prevention Study (EGPS). Randomized, double masked, controlled clinical trial. setting: Multicenter. study population: A total of 1,077 patients fulfilled a series of inclusion criteria, including intraocular pressure (IOP) 22 to 29 mm Hg, normal and reliable visual fields (VFs) and normal optic disks. intervention: Treatment with dorzolamide or placebo. main outcome measures: Glaucoma-related VF or optic disk changes. Clinical data were collected every six months during a five-year follow-up. Proportional hazards models were used to identify the factors that during follow-up (intercurrent factors) were associated with the development of OAG. In multivariate analyses, adjusting for treatment arms and baseline predictive factors, mean follow-up IOP reduction (hazard ratio [HR] 0.89, 95% confidence intervals [CI] 0.80 to 0.98), mean follow-up IOP (HR 1.12, 95% CI 1.03 to 1.22), area under the curve of IOP (mm Hg per year) (HR 1.09, 95% CI 1.06 to 1.12), disk hemorrhages (HR 1.97, 95% CI 1.21 to 3.22), and use of systemic diuretics (HR 2.41, 95% CI 1.12 to 5.19) were associated with the development of OAG. Baseline central corneal thickness, vertical cup/disk ratio, vertical cup/disk ratio asymmetry, and pattern standard deviation remained statistically significant. These results suggest the need for future investigations to better elucidate the role of systemic diuretics in the development of OAG, because IOP and disk hemorrhages have already been shown to be important intercurrent factors in the Ocular Hypertension Treatment Study (OHTS) and Early Manifest Glaucoma Trial (EMGT).

Central Corneal Thickness in the European Glaucoma Prevention Study

To measure central corneal thickness (CCT) within the participants of the European Glaucoma Prevention Study (EGPS). This study was designed to test if lowering intraocular pressure (IOP) by means of dorzolamide is able to prevent or delay conversion from ocular hypertension to glaucoma. Randomized, double-masked, controlled, observational clinical trial. Eight hundred fifty-four of 1077 ocular hypertensive participants within the EGPS were investigated. Four hundred twenty-nine patients were treated with dorzolamide and 425 patients received placebo. Treatment with dorzolamide or placebo (the vehicle of dorzolamide) in 1 or both eyes. Central corneal thickness as measured by ultrasound pachymetry (DGH-500 Pachette; DGH Technologies, Exton, PA). The CCT measurements were obtained in the morning before measuring IOP. Five measurements were taken from each eye of each patient within 5 minutes of application of anesthetic eye drops. Mean CCT was 572.6+/-37.4 microm (range, 458.5-695.6 microm). The CCT was higher in younger patients, male patients, and diabetic patients. Mean CCTs for the 429 patients receiving dorzolamide were 574.2+/-38.48 microm (range, 458.5-695.6 microm) and 571.0+/-36.21 microm (469.7-690.1 microm) for the 425 patients receiving placebo (P = 0.205). Central corneal thickness did not correlate with refraction, baseline IOP, or systemic hypertension. Central corneal thickness measurements within the EGPS were greater than those reported in other studies of normal eyes without ocular hypertension. Larger CCT measurements correlated with male gender, younger age, and diabetes.

Validated Prediction Model for the Development of Primary Open-Angle Glaucoma in Individuals with Ocular Hypertension

To test the validity and generalizability of the Ocular Hypertension Treatment Study (OHTS) prediction model for the development of primary open-angle glaucoma (POAG) in a large independent sample of untreated ocular hypertensive individuals and to develop a quantitative calculator to estimate the 5-year risk that an individual with ocular hypertension will develop POAG. A prediction model was developed from the observation group of the OHTS and then tested on the placebo group of the European Glaucoma Prevention Study (EGPS) using a z statistic to compare hazard ratios, a c statistic for discrimination, and a calibration chi2 for systematic overestimation/underestimation of predicted risk. The 2 study samples were pooled to increase precision and generalizability of a 5-year predictive model for developing POAG. The OHTS observation group (n = 819; 6.6 years' median follow-up) and EGPS placebo group (n = 500; 4.8 years' median follow-up). Data were collected on demographic characteristics, medical history, ocular examination visual fields (VFs), and optic disc photographs. Development of reproducible VF abnormality or optic disc progression as determined by masked readers and attributed to POAG by a masked end point committee. The same predictors for the development of POAG were identified independently in both the OHTS observation group and the EGPS placebo group-baseline age, intraocular pressure, central corneal thickness, vertical cup-to-disc ratio, and Humphrey VF pattern standard deviation. The pooled multivariate model for the development of POAG had good discrimination (c statistic, 0.74) and accurate estimation of POAG risk (calibration chi2, 7.05). The OHTS prediction model was validated in the EGPS placebo group. A calculator to estimate the 5-year risk of developing POAG, based on the pooled OHTS-EGPS predictive model, has high precision and will be useful for clinicians and patients in deciding the frequency of tests and examinations during follow-up and advisability of initiating preventive treatment.

Predictive Factors for Open-Angle Glaucoma among Patients with Ocular Hypertension in the European Glaucoma Prevention Study

To evaluate the predictive factors of open-angle glaucoma (OAG) in patients affected by ocular hypertension enrolled in the European Glaucoma Prevention Study (EGPS). Randomized, double-masked, controlled clinical trial. One thousand seventy-seven patients, > or =30 years old, were enrolled at 18 European centers. The patients met inclusion criteria: intraocular pressure, 22 to 29 mmHg; 2 normal and reliable visual fields (VFs) (on the basis of mean deviation and corrected pattern standard deviation [PSD]); and a normal optic disc, as determined by an optic disc reading center. Treatment with dorzolamide or a placebo (the vehicle of dorzolamide) in one or both eyes. Efficacy end points were VF and/or optic disc changes. Baseline demographic and clinical data were collected before randomization, except for corneal thickness measurements, which were determined during follow-up. Proportional hazards models were used to identify factors that predicted which participants in the EGPS had developed OAG. In multivariate analyses, factors that predicted the development of OAG included older age (hazard ratio [HR], 1.32; 95% confidence interval [CI], 1.04-1.69), larger vertical cup-to-disc (C/D) ratio (HR, 1.34; 95% CI, 1.14-1.58), larger vertical C/D ratio asymmetry (HR, 1.46; 95% CI, 1.11-1.93), higher PSD (HR, 1.66; 95% CI, 1.15-2.38), and lesser central corneal thickness (HR, 1.32; 95% CI, 1.05-1.67). Baseline age, vertical C/D ratio, vertical C/D ratio asymmetry, and PSD were good predictors of the onset of OAG in the EGPS. Central corneal thickness was found to be a powerful predictor of the development of OAG. The EGPS results agree with the findings of the Ocular Hypertension Treatment Study and support the need for a thorough evaluation of patients with ocular hypertension.

Treating Ocular Hypertension to Reduce Glaucoma Risk

When to treat the patient who presents with ocular hypertension has been a question that has 'stumped' the ophthalmic community for decades. Population-based studies and intervention trials have provided the basis for understanding why we consider treating such patients. Although the EGPS (European Glaucoma Prevention Study) did not demonstrate that reducing intraocular pressure (IOP) with dorzolamide prevented the onset of glaucoma compared with individuals receiving a placebo, the investigators of the OHTS (Ocular Hypertension Treatment Study) found that the treatment of ocular hypertension can be delayed with topical medication when treated patients were compared with an observation group. There are differences in inclusion criteria, study design and retention rates between the EGPS and the OHTS, which may have led to the discrepancies in outcomes between these two studies. These differences provide a basis for understanding the relevance of the findings of both trials to clinical practice. The clinician should consider key risk factors such as age, thin corneal thickness measurements, large cup-to-disc ratio and mean IOP when determining who should be treated. However, the ultimate decision of when to treat will be determined by other issues such as life expectancy, the general health of the patient and the number of risk factors. Clearly, the treatment of only high-risk patients with ocular hypertension should be considered.

Update prospektiver Glaukomstudien

Previously published prospective therapeutic intervention studies in ocular hypertension and glaucoma are summarized. The concept of intraocular pressure reduction was evaluated in normal tension glaucoma ["Early manifest glaucoma trial (EMGT)"], the "Collaborative normal-tension glaucoma study (CNTGS)" and ocular hypertension ["Ocular hypertensive study (OHTS)" as well as the "European glaucoma prevention study (EGPS)"]. Early open angle glaucoma patients were included in the EMGT trial as well as the "Collaborative initial glaucoma treatment study (CIGTS)", whereas advanced glaucoma patients were examined in the "Advanced glaucoma intervention study (AGIS)". The study design, the results and the conclusions will be highlighted in the text. The therapeutic concept of intraocular pressure reduction decreases the risk of progression by 50 % in normal tension glaucoma, ocular hypertension and early open angle glaucoma. The mean pressure reduction to 12 mmHg in advanced glaucoma abolished visual field progression. The natural course of the disease documented by the control groups is now known. Sensitive glaucoma progression detection is clinically available by glaucoma change probability maps (Humphrey-full threshold perimetry) used in the EMGT.