Efficacy and safety of travoprost/timolol vs dorzolamide/timolol in patients with open-angle glaucoma or ocular hypertension

Purpose: To compare the intraocular pressure- (IOP-) lowering efficacy of fixed combinations travoprost 0.004%/timolol 0.5% and dorzolamide 2%/timolol 0.5% in patients with ocular hypertension or open-angle glaucoma. Methods: In this prospective, multicenter, double-masked, randomized clinical trial, 319 qualifying patients received either travoprost/timolol once daily in the morning (n = 157) or dorzolamide/timolol twice daily (n = 162). IOP was assessed morning and evening at 2 and 6 weeks. The primary outcome measure was mean diurnal IOP. Results: Baseline mean IOP values were similar between groups. Mean pooled diurnal IOP was significantly lower in the travoprost/timolol group (16.5 mmHg ± 0.23) than in the dorzolamide/timolol group (17.3 mmHg ± 0.23; P = 0.011). Mean IOP was significantly lower in the travoprost/timolol group compared to the dorzolamide/timolol group at the 9 AM time point both at Week 2 (P = 0.006) and Week 6 (P = 0.002). The travoprost/timolol combination produced mean IOP reductions from baseline of 35.3% to 38.5%, while the dorzolamide/timolol combination produced mean IOP reductions from baseline of 32.5% to 34.5%. Conclusions: The fixed combination travoprost 0.004%/timolol 0.5% dosed once daily in the morning demonstrated superior mean diurnal IOP-lowering efficacy compared to dorzolamide 2%/timolol 0.5% dosed twice daily in patients with ocular hypertension or open-angle glaucoma.publishersversionPeer reviewe

24-h Efficacy of Glaucoma Treatment Options

Current management of glaucoma entails the medical, laser, or surgical reduction of intraocular pressure (IOP) to a predetermined level of target IOP, which is commensurate with either stability or delayed progression of visual loss. In the published literature, the hypothesis is often made that IOP control implies a single IOP measurement over time. Although the follow-up of glaucoma patients with single IOP measurements is quick and convenient, such measurements often do not adequately reflect the untreated IOP characteristics, or indeed the quality of treated IOP control during the 24-h cycle. Since glaucoma is a 24-h disease and the damaging effect of elevated IOP is continuous, it is logical that we should aim to understand the efficacy of all treatment options throughout the 24-h period. This article first reviews the concept and value of diurnal and 24-h IOP monitoring. It then critically evaluates selected available evidence on the 24-h efficacy of medical, laser and surgical therapy options. During the past decade several controlled trials have significantly enhanced our understanding on the 24-h efficacy of all glaucoma therapy options. Nevertheless, more long-term evidence is needed to better evaluate the 24-h efficacy of glaucoma therapy and the precise impact of IOP characteristics on glaucomatous progression and visual prognosis

Criteria for choosing clinically effective glaucoma treatment: A discussion panel consensus

AbstractBackground:In the clinical management of patients at risk for or diagnosed with primary open-angle glaucoma (POAG), the aim of medical treatment is to reduce intraocular pressure (IOP) and then maintain it over time at a level that preserves both the structure and function of the optic nerve.Objective:The objective of this report was to establish a consensus on the criteria that should be used to determine the characteristics of IOP-lowering medication.Methods:Discussion was held among a panel of 12 physicians considered to be experts in glaucoma to develop a consensus on the criteria used by them to determine the characteristics of the IOP-lowering medication chosen for initial monotherapy and adjunctive treatment of ocular hypertension (OHT) or POAG. Consensus development combined available evidence and the impressions of these physicians regarding the clinical effectiveness of IOP-lowering medication for OHT and POAG. Once the panel identified the criteria, the order of priority and the relative importance of these criteria were then established in the setting of 3 risk categories (low, medium, and high) for a patient to experience significant visual disability from glaucoma over their expected life span.Results:The panel identified 5 criteria to determine the characteristics of IOP-lowering medication for OHT and POAG: IOP-lowering effect, systemic adverse events (AEs), ocular tolerability, compliance/administration, and cost of treatment. IOP-lowering effect was consistently ranked as the highest priority and cost as the lowest. The priority of compliance/administration did not vary by clinical situation. Systemic AEs and ocular tolerability were ranked as higher priorities in initial monotherapy than in adjunctive treatment and ranked lower as the risk for visual disability increased. The priority given to the criteria used to determine clinical effectiveness varied both with the risk for functional vision loss from glaucoma and whether initial monotherapy or adjunctive treatment was being considered.Conclusion:Glaucoma treatment should be assessed with regard to the need not only to lower IOP but also to minimize systemic and ocular AEs, promote patient compliance, and minimize cost. The order of priority and relative importance given to these treatment criteria will vary as part of individualizing patient care

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gressed patients (1.3, p = 0.005). A multivariate regression analysis showed higher mean, peak and variance of IOP, number of glaucoma medications at the final visit and presence of a disc hemorrhage (n = 5) as independent risk factors for progression (p ^ 0.05). Conclusion: IOP reduction in XFG may be essential in reducing disease progression. The presence of disc hemorrhage in XFG may suggest an increased probability of progression despite treatment to within the normal IOP range

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.status: publishe

Macular versus nerve fibre layer versus optic nerve head imaging for diagnosing glaucoma at different stages of the disease: Multicenter Italian Glaucoma Imaging Study

PURPOSE: To compare the diagnostic accuracy of minimum rim width (MRW), peripapillary retinal nerve fibre layer (pRNFL) and multilayered macular analysis by Spectralis SD-OCT (Heidelberg Engineering, Germany) in discriminating perimetric glaucoma at different stages of the disease from healthy eyes. METHODS: In this multicentre, prospective, evaluation of diagnostic tests study, multilayered macular analysis and MRW and pRNFL were obtained from one eye of 197 glaucoma (76 early, 68 moderate and 53 advanced) and of 83 healthy controls from the Multicenter Italian Glaucoma Imaging Study (MIGIS). The reference standard for classifying eyes as glaucomatous and for staging the disease was the visual field. The main outcome measures were area under the ROC curve (AUC) and sensitivity at fixed specificity (95%). RESULTS: Average MRW and average pRNFL showed the highest and similar diagnostic accuracy in both the whole study population (AUC 0.968 and 0.939) and early glaucoma (AUC 0.956 and 0.929). Among the macular parameters, the three innermost retinal layers combined as the Ganglion Cell Complex provided the highest diagnostic accuracy (AUC 0.931) in the whole population, which was statistically similar to that of average pRNFL but inferior to that of average MRW. Compared to both average MRW and pRNFL, all macular parameters showed statistically significant lower accuracy in early glaucoma, but accuracy in moderate and advanced glaucoma showed no statistically significant differences among three protocols. CONCLUSION: The diagnostic accuracy of MRW, pRNFL and macular analysis by Spectralis SD-OCT is overall good. MRW and pRNFL analysis performs statistically and clinically better than macular analysis to discriminate early glaucoma from healthy eyes

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 :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 less than or equal to0.4). 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

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

To determine the reproducibility of the assessment for glaucomatous change in serial optic disc stereo-slides. Masked interobserver variability study. Serial optic disc stereo-slides from 40 patients. 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. Reproducibility in evaluating glaucomatous optic disc change. 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). 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