Evaluation of a Primary Open-Angle Glaucoma Prediction Model Using Long-term Intraocular Pressure Variability Data: A Secondary Analysis of 2 Randomized Clinical Trials.

Importance: The contribution of long-term intraocular pressure (IOP) variability to the development of primary open-angle glaucoma is still controversial. Objective: 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. Design, Setting, and Participants: 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. Exposures: 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. Main Outcomes and Measures: The C statistic was used to compare the predictive accuracy of multivariable landmark Cox proportional hazards regression models for the development of POAG. Results: 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. Conclusions and Relevance: 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.

Exploring the gap between diagnostic research outputs and clinical use of OCT for diagnosing glaucoma.

AIMS: To explore the gap between diagnostic research outputs and clinical use of optical coherence tomography (OCT) in glaucoma and assess the reliability of a specific reference database when applied to a morphological imaging parameter for diagnostic purposes. METHODS: Consecutive subjects enrolled in the Multicenter Italian Glaucoma Imaging Study (MIGIS) have been included in this cross-sectional, comparative evaluation of diagnostic tests study. Patients underwent measurement of global and sectorial peripapillary retinal nerve fibre thickness (pRNFL) and minimum rim width (MRW) by OCT. The sensitivity and specificity of reference-database categorical classifications were calculated by means of 2×2 tables and sensitivity was compared with that of the corresponding continuous parameter extracted from the receiver operating characteristic (ROC) curves by matching the specificity. RESULTS: 280 Caucasian subjects have been included. At matched specificities, the sensitivity of pRNFL categorical classifications was statistically similar to that of the corresponding continuous parameters, whereas the sensitivity of the MRW categorical classifications was significantly lower than that of the corresponding continuous parameters. CONCLUSIONS: The diagnostic accuracy of reference database classifications might be lower than that extrapolated from the ROC curves of continuous parameters used in diagnostic research. The gap between the accuracy of these two approaches may be used to estimate the reliability of a specific reference database when applied to a continuous parameter for diagnostic purposes.

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.

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.

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

PURPOSE: 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. PARTICIPANTS AND METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Exfoliative glaucoma: new evidence in the pathogenesis and treatment.

Exfoliation or pseudoexfoliation syndrome (PXF) is an age-related ocular and systemic disease in which abnormal extracellular material is produced and accumulates in many tissues. PXF is the most common identifiable cause of open-angle glaucoma (OAG). PXFG is a particularly aggressive type of OAG, which runs with a faster rate of progression and poorer response to medical therapy than primary OAG (POAG). The prevalence of the condition shows huge variations among different population, Scandinavian and Mediterranean race being the most affected. Many genetics and environmental factors are involved in the pathogenesis and remarkable progresses in understanding the involved factors have been achieved in the past years. Population-based studies have identified mutations on the lysil-oxidase-like 1(LOXL1) gene as a risk factor for PXFS. Environmental and behavioral factors such as latitude of residence, caffeine intake, and vitamins deficiency are under investigation for a possible involvement in determining the disease in genetically predisposed individuals. Treatment options are similar to those recommended for POAG. Exfoliation syndrome predisposes to capsular rupture, zonular dehiscence, and vitreous loss during cataract extraction. Laser trabeculoplasty has been demonstrated to show good clinical outcomes in PXF patients. A review of the current literature and scientific evidences on pathogenesis and treatment is presented.

Predictive value of heidelberg retina tomograph parameters for the development of glaucoma in the European glaucoma prevention study.

PURPOSE: 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). DESIGN: Retrospective analysis of a prospective, randomized, multicenter, double-masked, controlled clinical trial. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

Evaluation of retinal nerve fiber layer thickness measurements for glaucoma detection: GDx ECC versus spectral-domain OCT.

BACKGROUND: To assess the ability of retinal nerve fiber layer (RNFL) thickness measurements obtained using GDx-enhanced corneal compensation (ECC) or spectral-domain optical coherence tomography (RTVue), and that of ganglion cell complex (GCC) scan available on RTVue, to detect glaucoma. METHODS: One randomly selected eye of 205 subjects (70 normal, 65 ocular hypertension, and 70 glaucoma) underwent a complete clinical and instrumental examination. RTVue spectral-domain optical coherence tomography was used to assess RNFL thickness and GCC parameters, GDx ECC to assess RNFL thickness. Areas under the receiver operating characteristic curves (AUCs) and sensitivity of the RNFL and GCC parameters were calculated at a fixed specificity of 95%, and the diagnostic abilities of the RNFL values obtained using the 2 instruments were compared. We also compared the results obtained in the normal, ocular hypertensive, and glaucomatous subjects. RESULTS: Best GDx RNFL parameter was nerve fiber indicator (NFI) (AUC 0.99, sensitivity 96%); the best RTVue parameters were average (AUC 0.98, sensitivity 90%), inferior-temporal (AUC 0.97, sensitivity 89%), and superior-temporal RNFL thickness (AUC 0.96, sensitivity 87%). There were no significant differences between the 2 devices (P>0.05). Best GCC parameters were focal loss volume (AUC 0.98, sensitivity 91%) and global loss volume (AUC 0.96, sensitivity 87%). CONCLUSIONS: GDx ECC and RTVue show a very good diagnostic ability to detect glaucoma. Most of the RNFL parameters had high AUCs and sensitivities. The diagnostic validity of GCC was comparable with that of the RNFL parameters, and they may be very useful in detecting RNFL damage.

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

PURPOSE: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

Relationship between intraocular pressure and glaucoma onset and progression.

Open-angle glaucoma is a multifactorial disease, and among the several risk factors, a high intraocular pressure represents the most consistent and the only one that can be modified in order to provide a significant impact over the course of the disease. High intraocular pressure is significantly associated to the onset and the progression of open angle glaucoma, and the results of several randomised controlled clinical trials have consistently attributed a higher 10% higher risk for both the development and the progression of the disease to each higher single mmHg. Intraocular pressure has been studied in terms of mean value and short-term and long-term fluctuations. As of today the mean value represents the most significant factor whereas the importance of both short-term and long-term fluctuations is still debated.

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.

BACKGROUND: Primary 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. METHOD: In 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. RESULT: The 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. CONCLUSION: LCA 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.

Risk factors associated with progression in exfoliative glaucoma patients.

PURPOSE: To evaluate exfoliative glaucoma (XFG) patients over 5 years, determining risk factors associated with progression or non-progression of glaucoma. METHODS: A retrospective, observational study. Patients were chosen from consecutive charts and data collected from each available visit included in the follow-up period. Data were abstracted for non-progressed XFG patients for 5 years and for progressed patients until glaucoma worsened. Progression was determined from patient records and by disc photographs. RESULTS: There were 71 (53%) progressed and 63 (47%) non-progressed XFG patients.Baseline parameters demonstrated worse visual field damage (p=0.014) and more prescribed medicines (p=0.03) in progressed patients. The mean intraocular pressure (IOP) for progressed patients was 18.7±4.3 and 17.3±3.4 mm Hg for non-progressed patients (p=0.047). The mean IOP that best separated the groups was 17 mm Hg with 60% staying non-progressed at or below this level and 30% above this level. At the last visit, progressed patients had more medicines prescribed (1.7) than non-progressed 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.

A Joint Model for Prognostic Effect of Biomarker Variability on Outcomes: long-term intraocular pressure (IOP) fluctuation on the risk of developing primary open-angle glaucoma (POAG).

Primary open-angle glaucoma (POAG) is among the leading causes of blindness in the United States and worldwide. While numerous prospective clinical trials have convincingly shown that elevated intraocular pressure (IOP) is a leading risk factor for the development of POAG, an increasingly debated issue in recent years is the effect of IOP fluctuation on the risk of developing POAG. In many applications, this question is addressed via a "naïve" two-step approach where some sample-based estimates (e.g., standard deviation) are first obtained as surrogates for the "true" within-subject variability and then included in Cox regression models as covariates. However, estimates from two-step approach are more likely to suffer from the measurement error inherent in sample-based summary statistics. In this paper we propose a joint model to assess the question whether individuals with different levels of IOP variability have different susceptibility to POAG. In our joint model, the trajectory of IOP is described by a linear mixed model that incorporates patient-specific variance, the time to POAG is fit using a semi-parametric or parametric distribution, and the two models are linked via patient-specific random effects. Parameters in the joint model are estimated under Bayesian framework using Markov chain Monte Carlo (MCMC) methods with Gibbs sampling. The method is applied to data from the Ocular Hypertension Treatment Study (OHTS) and the European Glaucoma Prevention Study (EGPS), two large-scale multi-center randomized trials on the prevention of POAG.

Diagnostic validity of optic disc and retinal nerve fiber layer evaluations in detecting structural changes after optic neuritis.

PURPOSE: To assess the diagnostic validity of morphometric examination of the optic disc and retinal nerve fiber layer (RNFL) thickness to detect permanent structural changes after retrobulbar optic neuritis (ON). DESIGN: Evaluation of a diagnostic test. PARTICIPANTS: Twenty-five patients with a history of retrobulbar ON and 29 disease-free controls. METHODS: The optic discs were evaluated by means of confocal scanning laser ophthalmoscopy (Heidelberg Retinal Tomograph [HRT III]), and RNFL thickness by means of scanning laser polarimetry (GDx), and optical coherence tomography (OCT). Vision function was assessed in all subjects by testing visual acuity, contrast sensitivity, color vision, visual field (VF), and visual evoked potentials (VEPs). Statistical comparisons were made between the affected (ON) and unaffected eyes (non-ON) of the patients with ON, and between these eyes and control eyes (Mann-Whitney test and Wilcoxon's test). Receiver operating characteristic (ROC) curves, and sensitivity and specificity in discriminating ON from control eyes, were calculated for the significant parameters. Correlations between the tests were calculated by means of Spearman's correlation coefficient. MAIN OUTCOME MEASURES: We compared OCT, GDx, HRT, and visual testing results in ON eyes versus control eyes. RESULTS: All of the visual function test parameters and RNFL thickness (GDx and OCT) were significantly different between the ON eyes and both the non-ON and control eyes (P<0.01), and there were significant differences in some GDx parameters between the non-ON and control eyes. There were no significant differences in the HRT parameters. The ROC curves indicated that the greatest diagnostic validity was associated with the GDx nerve fiber indicator (AUC, 0.92; sensitivity, 0.80; specificity, 0.97 using a cutoff point of 20.5 between ON and non-ON eyes), and OCT temporal thickness (AUC, 0.92; sensitivity, 0.72; specificity, 0.95 using a cutoff point of 51.5 microm). CONCLUSIONS: When investigating permanent damage after ON, RNFL thickness is a promising biomarker. The GDx and OCT are reliable, noninvasive, user-friendly devices; both show good diagnostic validity and good correlations with functional tests in discriminating affected from unaffected eyes. Retinal nerve fiber layer thinning in non-ON eyes should be further studied as a possible subclinical indicator of disease.

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.

Risk factors for glaucoma onset and progression.

In this review, we distinguish among risk factors associated with the development of open-angle glaucoma in individuals with healthy eyes, predictive determinants for the development of open-angle glaucoma in subjects with ocular hypertension, and prognostic factors for the progression of open-angle glaucoma in individuals who already have the disease. We primarily reviewed recent longitudinal population-based epidemiological studies, prospectively planned clinical trials, and cohort studies. Risk factors consistently associated with the development of open-angle glaucoma in individuals with healthy eyes include older age and an approximately 1 mm Hg increase in intraocular pressure (IOP) at baseline. Family history for open-angle glaucoma may be associated with the development of open-angle glaucoma as well. Predictive factors for the development of open-angle glaucoma in individuals with ocular hypertension may be older age, thinner central corneal thickness, higher cup-to-disk ratios of the optic disc, and higher pattern standard deviation values on the Humphrey automated perimeter at baseline. Given multi-center trials that showed similar predictive factors for the development of open-angle glaucoma in individuals with ocular hypertension, a calculator is available to clinicians for assessing the 5-year likelihood of developing open-angle glaucoma in ocular hypertensive patients with certain characteristics. Prognostic factors for the progression of open-angle glaucoma in individuals who already have the condition include older age at baseline, higher IOP at baseline, and thinner central conreal thickness. Self-report of diabetes may be associated with open-angle glaucoma progression. In conclusion, the only modifiable factor associated with open-angle glaucoma that has been consistently identified is elevated baseline IOP. Future research needs to evaluate the importance of others modifiable factors such as IOP fluctuation or nutritional factors.

Effects of the timolol-dorzolamide fixed combination and latanoprost on circadian diastolic ocular perfusion pressure in glaucoma.

PURPOSE: To evaluate the effect of the timolol-dorzolamide fixed combination (TDFC) and latanoprost 0.005% on 24-hour intraocular pressure (IOP), systolic (SBP) and diastolic (DBP) blood pressure, and diastolic ocular perfusion pressure (DOPP) in patients with primary open-angle glaucoma (POAG). METHODS: This was an institutional, randomized clinical trial. After a 24-hour assessment without treatment, 27 previously untreated patients with POAG were randomized to 6 weeks' treatment with twice-daily TDFC (8 AM and 8 PM) followed by once-daily latanoprost 0.005% (8 PM), or vice versa. One eye was analyzed per patient. The mean values of IOP, DBP, SBP, and DOPP (difference between DBP and IOP) were recorded at each time point, and the 24-hour data are the mean values of each patient's measurements over the 24-hour period. The differences between the values of the first treatment period and the baseline and the second treatment period and washout were calculated and analyzed by means of an analysis of variance model that tested the effects of sequence and treatment. RESULTS: Both treatments significantly reduced 24-hour IOP (P < 0.0001), but TDFC led to lower 24-hour pressure (mean +/- SD: 15.4 +/- 1.9 vs. 16.7 +/- 1.7 mm Hg; P = 0.004). Latanoprost did not lead to any significant reduction in mean 24-hour SBP and DBP (SBP: P = 0.952; DBP: P = 0.831), but TDFC did (SBP and DBP: P < 0.0001). Both treatments significantly increased 24-hour DOPP (P < 0.0001), with no difference between the two medications (P = 0.09). CONCLUSIONS: In previously untreated patients with POAG, TDFC, and latanoprost equally enhanced 24-hour DOPP: the former by counteracting the decrease in DBP with a substantial reduction in IOP and the latter by not affecting DBP and significantly reducing IOP. (isrctn.org number, ISRCTN67123277.).