Cardiorenal outcomes, kidney function, and other safety outcomes with ertugliflozin in older adults with type 2 diabetes (VERTIS CV): secondary analyses from a randomised, double-blind trial.

BACKGROUND: VERTIS CV was a randomised, double-blind, placebo-controlled, parallel-group, multicentre cardiovascular outcomes trial that evaluated the cardiovascular efficacy and safety of ertugliflozin in adults with type 2 diabetes and atherosclerotic cardiovascular disease. The primary objective of VERTIS CV was to show non-inferiority of ertugliflozin to placebo with respect to the primary outcome, major adverse cardiovascular events (a composite of death from cardiovascular causes, non-fatal myocardial infarction, or non-fatal stroke). The analyses reported here aimed to assess cardiorenal outcomes, kidney function, and other safety outcomes with ertugliflozin in older adults with type 2 diabetes and atherosclerotic cardiovascular disease compared with younger participants. METHODS: VERTIS CV was done at 567 centres in 34 countries. Participants (aged ≥40 years) with type 2 diabetes and atherosclerotic cardiovascular disease were randomly assigned (1:1:1) to once-daily ertugliflozin 5 mg, ertugliflozin 15 mg, or placebo in addition to background standard-of-care treatment. Random assignment was done with the use of an interactive voice-response system. The study outcomes were major adverse cardiovascular events, hospitalisation for heart failure or cardiovascular death, cardiovascular death, hospitalisation for heart failure, prespecified kidney composite outcomes, kidney function, and other assessments of safety. Cardiorenal outcomes, kidney function, and safety outcomes were evaluated by baseline age (≥65 years and <65 years [prespecified] and ≥75 years and <75 years [post hoc]). The study is registered with ClinicalTrials.gov, NCT01986881. FINDINGS: Between Dec 13, 2013, and July 31, 2015, and between June 1, 2016, and April 14, 2017, 8246 adults with type 2 diabetes and atherosclerotic cardiovascular disease were recruited to the study and randomly assigned. 2752 patients were assigned to ertugliflozin 5 mg, 2747 patients to ertugliflozin 15 mg, and 2747 patients to placebo. 8238 participants received at least one dose of ertugliflozin 5 mg, ertugliflozin 15 mg, or placebo. 4145 (50·3%) of 8238 participants were aged 65 years and older, including 903 (11·0%) participants aged 75 years and older. 5764 (70·0%) of 8238 participants were male and 2474 (30·0%) were female, and 7233 (87·8%) of 8238 participants were White, 497 (6·0%) were Asian, 235 (2·9%) were Black, and 273 (3·3%) were classified as other. The mean estimated glomerular filtration rate (eGFR) was lower and the type 2 diabetes duration longer for those aged 65 years and older versus those younger than 65 years, and for those aged 75 years and older versus those younger than 75 years. Cardiovascular outcomes were more common in the older age subgroups than in the younger age subgroups. Similar to the overall VERTIS CV cohort, ertugliflozin did not increase the risk of major adverse cardiovascular events, cardiovascular death or hospitalisation for heart failure, cardiovascular death alone, or the kidney composite outcome (using doubling of serum creatinine, dialysis or transplantation, or kidney death), and reduced the risk of hospitalisation for heart failure and the exploratory kidney composite outcome (using a 40% sustained eGFR decrease, dialysis or transplantation, or kidney death) in the older age subgroups (pinteraction>0·05 for outcomes assessed). A slower decline in eGFR and a smaller increase in the urine albumin-to-creatinine ratio were observed over time in all age subgroups taking ertugliflozin compared with placebo. Across age subgroups, safety outcomes were consistent with the known profile of ertugliflozin. INTERPRETATION: The effects of ertugliflozin on cardiorenal outcomes, kidney function, and safety outcomes were generally similar across age subgroups. These results have the potential to help clinical decision making by providing a longer-term evaluation of the cardiorenal safety and overall tolerability of ertugliflozin in a large population of older adults. FUNDING: Merck Sharp & Dohme LLC, a subsidiary of Merck & Co, Inc, Rahway, NJ, USA in collaboration with Pfizer Inc, New York, NY, USA.

Comparison of the efficacy and tolerability of preservative-free and preservative-containing formulations of the dorzolamide/timolol fixed combination (COSOPT™) in patients with elevated intraocular pressure in a randomized clinical trial.

BACKGROUND: The aim of this study was to compare the efficacy and tolerability of preservative-free (PF) and preservative-containing (PC) formulations of the dorzolamide/timolol fixed combination (COSOPT™) in patients with elevated intraocular pressure (IOP). METHODS: A parallel, randomized, double-masked study was conducted. After a 3-week run-in on timolol, patients with ocular hypertension, as confirmed by an IOP ≥22 mmHg, were randomized 1:1 to receive PF or PC dorzolamide/timolol twice daily for 12 weeks. IOP was measured at hour 0 (drug trough) and hour 2 (drug peak) at baseline (last day of 3-week timolol run-in), and weeks 2, 6 and 12. RESULTS: A total of 261 patients were randomized. Mean baseline IOPs were 23.7 mmHg for both treatments at hour 0 and 21.2 mmHg for PF dorzolamide/timolol and 21.4 mmHg for PC dorzolamide/timolol at hour 2. At all study time points (trough and peak at weeks 2, 6, and 12), the difference between treatments in mean change from baseline IOP was <0.5 mmHg. The 95% confidence intervals for the estimated treatment difference (PF minus PC) in mean change from baseline IOP at week 12 was -0.86 to 0.23 mmHg for trough (primary endpoint) and -0.39 to 0.67 mmHg for peak (secondary endpoint). The most common adverse events were ocular burning/stinging, reported by 16.0% and 21.5% of patients receiving PF and PC dorzolamide/timolol respectively, and taste perversion, reported by 3.1% and 5.4% of patients receiving PF and PC dorzolamide/timolol respectively. CONCLUSIONS: In patients with elevated IOP, PF and PC dorzolamide/timolol were equivalent in efficacy for change in trough and peak IOP, and had generally similar tolerability.

Intercurrent factors associated with the development of open-angle glaucoma in the European glaucoma prevention study.

PURPOSE: 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). DESIGN: Randomized, double masked, controlled clinical trial. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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).

Validated prediction model for the development of primary open-angle glaucoma in individuals with ocular hypertension.

OBJECTIVE: 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. DESIGN: 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. PARTICIPANTS: The OHTS observation group (n = 819; 6.6 years' median follow-up) and EGPS placebo group (n = 500; 4.8 years' median follow-up). TESTING: Data were collected on demographic characteristics, medical history, ocular examination visual fields (VFs), and optic disc photographs. MAIN OUTCOME MEASURE: Development of reproducible VF abnormality or optic disc progression as determined by masked readers and attributed to POAG by a masked end point committee. RESULTS: 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). CONCLUSIONS: 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.

OBJECTIVE: To evaluate the predictive factors of open-angle glaucoma (OAG) in patients affected by ocular hypertension enrolled in the European Glaucoma Prevention Study (EGPS). DESIGN: Randomized, double-masked, controlled clinical trial. PARTICIPANTS: 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. INTERVENTION: Treatment with dorzolamide or a placebo (the vehicle of dorzolamide) in one or both eyes. MAIN OUTCOME MEASURES: 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. RESULTS: 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). CONCLUSIONS: 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.

Central corneal thickness in the European Glaucoma Prevention Study.

PURPOSE: 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. DESIGN: Randomized, double-masked, controlled, observational clinical trial. PARTICIPANTS: 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. INTERVENTION: Treatment with dorzolamide or placebo (the vehicle of dorzolamide) in 1 or both eyes. MAIN OUTCOME MEASURES: 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. RESULTS: 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. CONCLUSION: 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.

A randomized trial assessing dorzolamide in patients with glaucoma who are younger than 6 years.

OBJECTIVE: To evaluate dorzolamide hydrochloride in patients younger than 6 years who have an elevated intraocular pressure or glaucoma. DESIGN: A 3-month, controlled, randomized, double-masked, multicenter, clinical trial. Patients were randomized to 2% dorzolamide 3 times daily or timolol maleate gel-forming solution (0.25% for patients <2 years and 0.5% for patients > or =2 but <6 years) once daily plus placebo twice daily. If the intraocular pressure was not controlled through monotherapy, younger patients received concomitant dorzolamide 3 times daily and 0.25% timolol gel-forming solution once daily and older patients received a fixed combination of 2% dorzolamide and 0.5% timolol twice daily. The primary safety variable was the proportion of patients who discontinued therapy for a drug-related adverse experience. Intraocular pressure reduction was a secondary measure. RESULTS: One younger patient (1.8%) of 56 randomized to dorzolamide discontinued concomitant therapy because of bradycardia. Two older patients (3.0%) of 66 discontinued dorzolamide because of ocular adverse experiences. The most frequent ocular adverse experiences were discharge and ocular hyperemia (younger cohort) and ocular hyperemia and burning/stinging (older cohort). At week 12, the mean change in intraocular pressure for dorzolamide was statistically significant from baseline (-7.3 mm Hg [-20.6%] and -7.1 mm Hg [-23.3%]) in the younger and older cohorts, respectively; P<.001 for both. CONCLUSION: Dorzolamide was generally well tolerated and demonstrated efficacy for up to 3 months in patients younger than 6 years.

Efficacy of the dorzolamide/timolol fixed combination versus latanoprost in the treatment of ocular hypertension or glaucoma: combined analysis of pooled data from two large randomized observer and patient-masked studies.

In previous analyses of primary efficacy data from two randomized clinical trials, standard dosing regimens of the dorzolamide/timolol fixed combination (COSOPT) and latanoprost (XALATAN) were shown to have equivalent efficacy with regard to reduction in mean daytime diurnal intraocular pressure (IOP). We performed additional post hoc analyses of pooled data from these studies to compare further the efficacy of the two treatments. The studies used identical 3-month, parallel group, randomized, observer-masked and patient-masked, multicenter designs. Patients with a baseline IOP > or = 24 mm Hg were randomized to either the 2% dorzolamide/0.5% timolol combination eye drops twice daily (n = 273) or 0.005% latanoprost eye drops once daily (n = 271). The IOP measurements were made at 8 AM, 10 AM, 2 PM, and 4 PM at the baseline visit and then on each of the 3 monthly assessment days. The following measures were analyzed on a post hoc basis: 1) percentages of patients meeting target levels of IOP reduction; 2) mean IOP reduction in those patients with high IOP (> or =30 mmHg) at baseline; 3) mean IOP at each of the assessment time points during a day. A total of 259 patients in the dorzolamide/timolol group and 268 patients in the latanoprost group were included in the efficacy analysis. At 3 months, both treatments showed similar efficacy with regard to the percentages of patients who achieved target levels of IOP reduction (e.g., 40% IOP reduction in 15% of dorzolamide/timolol combination patients and 13% of latanoprost patients), mean IOP reduction in those patients with high IOP at baseline (dorzolamide/ timolol combination, 12.5 mmHg, latanoprost, 12.6 mmHg), and mean IOP at each time point during the day. By the measures used in this analysis, the dorzolamide/timolol combination and latanoprost were equally effective at lowering IOP in patients with ocular hypertension or glaucoma.

Dynamic contrast enhanced MRI in patients with diabetic macular edema: initial results.

To assess the ability of dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) to detect blood retinal barrier (BRB) damage in patients with diabetic macular edema (DME). DCE-MRI with 0.1 mmol Gd-DTPA was used to measure BRB permeability in 10 healthy and visually normal subjects and eight patients with DME, including five patients with non-clinically significant (NCS) DME and three patients with clinically significant (CS) DME. For each subject, the enhancement of the MRI signal intensity in the pre-macular vitreous was measured as a function of time following contrast injection. A linear regression analysis was performed on each subject and the slopes of the contrast enhancement functions were compared. The DCE-MRI procedure was well tolerated by all 18 subjects. However, in four subjects, excessive eye movements resulted in spurious results. Consequently, 78% (14/18) of the subjects provided usable data. The mean slope of the control group was not significantly (p>0.05) different from zero (i.e. signal intensity in the pre-macular vitreous space was constant as a function of time post-contrast injection). For the diabetic patients, the average slope of the contrast enhancement function was significantly greater than in the control group (p<0.01). Furthermore, for both diabetic sub-groups, the average slopes were greater (p<0.05) than that for the control group but not significantly (p>0.05) different from each other. This 'proof of concept' study demonstrated that DCE-MRI detects passive leakage through the BRB in diabetic patients with either NCS or CS macular edema. In future studies, DCE-MRI may be useful for early quantitative evaluation of drug treatment effects in patients with DME.

Results of the European Glaucoma Prevention Study.

OBJECTIVE: The European Glaucoma Prevention Study (EGPS) seeks to evaluate the efficacy of reduction of intraocular pressure (IOP) by dorzolamide in preventing or delaying primary open-angle glaucoma (POAG) in patients affected by ocular hypertension (OHT). DESIGN: Randomized, double-masked, controlled clinical trial. PARTICIPANTS: One thousand eighty-one patients (age, > or =30 years) were enrolled by 18 European centers. The patients fulfilled a series of inclusion criteria, including: IOP 22 to 29 mmHg; 2 normal and reliable visual fields (on the basis of mean deviation and corrected pattern standard deviation or corrected loss variance of standard 30/II Humphrey or Octopus perimetry); normal optic disc as determined by the Optic Disc Reading Center. INTERVENTION: Patients were randomized to treatment with dorzolamide or placebo (the vehicle of dorzolamide). MAIN OUTCOME MEASURES: Efficacy end points were visual field, optic disc changes, or both. A visual field change during follow-up had to be confirmed by 2 further positive tests. Optic disc change was defined on the basis of the agreement of 2 of 3 independent observers evaluating optic disc stereo slides. The safety end point was an IOP of more than 35 mmHg on 2 consecutive examinations. RESULTS: During the course of the study, the mean percent reduction in IOP in the dorzolamide group was 15% after 6 months and 22% after 5 years. Mean IOP declined by 9% after 6 months and by 19% after 5 years in the placebo group. At 60 months, the cumulative probability of converting to an efficacy end point was 13.4% in the dorzolamide group and 14.1% in the placebo group (hazard ratio, 0.86; 95% confidence interval [CI], 0.58-1.26; P = 0.45). The cumulative probability of developing an efficacy or a safety end point was 13.7% in the dorzolamide group and 16.4% in the placebo group (hazard ratio, 0.73; 95% CI, 0.51-1.06; P = 0.1). CONCLUSIONS: Dorzolamide reduced IOP by 15% to 22% throughout the 5 years of the trial. However, the EGPS failed to detect a statistically significant difference between medical therapy and placebo in reducing the incidence of POAG among a large population of OHT patients at moderate risk for developing POAG, because placebo also significantly and consistently lowered IOP.

Efficacy and tolerability of the dorzolamide 2%/timolol 0.5% combination (COSOPT) versus 0.005% (XALATAN) in the treatment of ocular hypertension or glaucoma: results from two randomized clinical trials.

PURPOSE: To compare the efficacy of the fixed dorzolamide 2%/timolol 0.5% combination (COSOPT) versus latanoprost 0.005% (XALATAN). METHODS: Two 3-month, parallel group, randomized, observer-masked and patient-masked, multicentre, clinical trials were performed in patients with ocular hypertension or open-angle glaucoma. Study 1 (n=256) was conducted in the United States and Study 2 (n=288) was conducted in Europe/Israel. Patients could be included whether or not they were currently taking ocular hypotensive therapy, and regardless of the effectiveness of any previous therapy. Patients were washed out from their usual ocular hypotensive medications and then those with a baseline intraocular pressure (IOP) >/= 24 mmHg were randomized to either the dorzolamide/timolol combination eye drops twice daily or latanoprost eye drops once daily in both eyes. Efficacy was assessed by daytime diurnal IOP (the mean of measurements made at 0800, 1000, 1400 and 1600 h). RESULTS: At baseline, the mean daytime diurnal IOP was 26.1 mmHg in the dorzolamide/timolol combination group versus 25.6 mmHg in the latanoprost group in Study 1, and 25.3 mmHg in the dorzolamide/timolol combination group versus 24.7 mmHg in the latanoprost group in Study 2. After 3 months, the mean daytime diurnal IOP was 18.9 mmHg for the dorzolamide/timolol combination versus 18.4 mmHg for latanoprost in Study 1, and 17.4 mmHg for the dorzolamide/timolol combination versus 17.5 for latanoprost in Study 2. The difference between treatments in mean IOP change at 3 months was -0.04 mmHg [95% confidence interval (CI) -0.85, 0.77] in Study 1, and -0.57 mmHg (95% CI -1.31, 0.16) in Study 2. The probability that the true difference lay between -1.5 and 1.5 mmHg, the predefined bounds for equivalence, was >0.950 in both studies. Both treatments were well tolerated over 3 months, although ocular stinging occurred more frequently with the dorzolamide/timolol combination. CONCLUSIONS: The dorzolamide/timolol combination and latanoprost were equally effective at lowering IOP.

Reproducibility of evaluation of optic disc change for glaucoma with stereo optic disc photographs.

PURPOSE: To determine the reproducibility of the assessment for glaucomatous change in serial optic disc stereo-slides. DESIGN: Masked interobserver variability study. PARTICIPANTS: Serial optic disc stereo-slides from 40 patients. METHODS: Three independent ophthalmologists evaluated for change a set of two serial 20 degrees optic disc color stereo-slides of 40 patients. This test set was not from European Glaucoma Prevention Study (EGPS) patients. Each observer performed two evaluations at least 30 days apart and was masked from the temporal sequence of the slides and his or her previous evaluation. Each patient was graded as changed or stable by two-out-of-three agreement. A kappa statistic was used to calculate the intra- and interobserver reproducibility as well as the assignment reproducibility (first consensus versus second consensus). The same procedure was followed to test the reproducibility when another experienced ophthalmologist was added to one of the three reading centers. MAIN OUTCOME MEASURES: Reproducibility in evaluating glaucomatous optic disc change. RESULTS: The intraobserver reproducibility (95% confidence interval [CI]) in the evaluation of change ranged between 0.79 (0.45-1.14) and 1.00 (0.69-1.31). The interobserver reproducibility (95% CI) in the evaluation of change ranged between 0.45 (0.15-0.75) and 0.75 (0.44-1.06). The assignment reproducibility (first consensus versus second consensus in the evaluation of change) between the senior EGPS readers was 0.94 (0.63-1.25). The assignment reproducibility when another experienced ophthalmologist replaced one of the readers was 0.94 (0.63-1.25). CONCLUSIONS: The assignment reproducibility of three expert readers looking for glaucomatous change in serial optic disc stereo-slides was excellent. It remained so when one of the three experts was replaced by another experienced reader.

The European glaucoma prevention study design and baseline description of the participants.

OBJECTIVES: The European Glaucoma Prevention Study seeks to evaluate the efficacy of reducing intraocular pressure (IOP), with dorzolamide to prevent or delay patients affected by ocular hypertension from developing primary open-angle glaucoma. DESIGN: Randomized, double-blinded, controlled clinical trial. PARTICIPANTS: Patients (age > or =30 years) were enrolled from 18 European centers. The patients fulfilled a series of inclusion criteria including the measurements of IOP (22-29 mmHg), two normal and reliable visual fields (VFs) (on the basis of mean defect and corrected pattern standard deviation/corrected loss of variance of standard 30/II Humphrey or Octopus perimetry), and normal optic disc as determined by the Optic Disc Reading Center (vertical and horizontal cup-to-disc ratios; asymmetry between the two eyes < or =0.4). INTERVENTION: Patients were randomized to the treatment with dorzolamide or a placebo. MAIN OUTCOME MEASURES: End points are VF and/or optic disc changes. A VF change during the follow-up must be confirmed by two further positive tests. Optic disc change is defined by the agreement of two out of three independent observers evaluating optic disc stereo-slides. RESULTS: One thousand seventy-seven subjects were randomized between January 1, 1997 and May 31, 1999. The mean age was 57.03 +/- 10.3 years; 54.41% were women and 99.9% were Caucasian. Mean IOP was 23.6 +/- 1.6 mmHg in both eyes. Mean visual acuity was 0.97 +/- 0.11 in both eyes; mean refraction was 0.23 +/- 1.76 diopters in the right eye and 0.18 +/- 1.79 diopters in the left eye. Previous use of medication for ocular hypertension was reported by 38.4% of the patients, systemic hypertension by 28.1%, cardiovascular diseases by 12.9%, and diabetes mellitus by 4.7%. The qualifying VFs were normal and reliable according to protocol criteria. CONCLUSIONS: The mean IOP of the patients enrolled in the European Glaucoma Prevention Study is consistent with the estimated mean IOP (within the range of 22-29 mmHg) found in a large sample of the European population. The European Glaucoma Prevention Study should be able to better address the clinical question of whether pharmacological reduction of IOP (by means of dorzolamide) in ocular hypertension patients at moderate risk for developing primary open-angle glaucoma effectively lowers the incidence of primary open-angle glaucoma.

Visual function after surgery for early cataract

Glare disability and contrast sensitivity loss can be present in cataract patients with minimally reduced visual acuity. Objective and subjective visual function was analyzed in 72 patients (mean visual acuity = 20/40) before and after cataract surgery. Following surgery, most subjects regained normal function in all tests. Improvement in contrast sensitivity and reduction of glare disability were independent of preoperative visual acuity. Subjective improvement in visual function was predicted by acuity and contrast sensitivity tests