Advanced Glaucoma Intervention Study Research Articles

Baseline Prognostic Factors Predict Rapid Visual Field Deterioration in Glaucoma

To investigate baseline prognostic factors predicting rapid deterioration of the visual field in primary open-angle glaucoma patients. Seven hundred sixty-seven eyes of 566 glaucoma patients from the Advanced Glaucoma Intervention Study (AGIS) and the clinical database from Jules Stein Eye Institute's Glaucoma Division were included. The rates of decay at each visual field test location were calculated with pointwise exponential regression analysis (PER), and the rates were separated into faster and slower components for each series. Subjects with a faster component decay rate (≥ 36%/y) were defined as rapid progressors. Sex, race, age, visual acuity, intraocular pressure, mean deviation (MD), number of medications, use of diabetic or hypertension medications, and vertical cup-to-disc ratio at baseline were entered in a multivariable prognostic logistic regression model. The average (± SD) MD was -8.02 (± 6.13), and the average age was 68.64 (± 11.71) years for the study group. Two hundred twenty-two eyes (28.9%) were identified as rapid progressors. The following baseline factors were predictors of faster deterioration: worse MD (P < 0.001, odds ratio [OR]: 1.11; 95% confidence interval [CI]: 1.07-1.15), larger vertical cup-to-disc ratio (P = 0.001, OR: 1.23; 95% CI: 1.09-1.39), and older age (P = 0.02, OR: 1.24; 95% CI: 1.04-1.48). After excluding the variables related to glaucoma severity at baseline (baseline MD and baseline vertical cup-to-disc ratio), the likelihood of being a rapid progressor was 54% greater in African Americans than in Caucasians (P = 0.03, OR: 1.55; 95% CI: 1.06-2.27). Patients with more severe glaucomatous damage, as measured by both visual field or optic disc cupping and older age, are at highest risk for rapid worsening of the disease, as are African Americans compared to Caucasians. More aggressive treatment of such patients should be considered to prevent visual disability.

Using Filtered Forecasting Techniques to Determine Personalized Monitoring Schedules for Patients with Open-Angle Glaucoma

To determine whether dynamic and personalized schedules of visual field (VF) testing and intraocular pressure (IOP) measurements result in an improvement in disease progression detection compared with fixed interval schedules for performing these tests when evaluating patients with open-angle glaucoma (OAG). Secondary analyses using longitudinal data from 2 randomized controlled trials. A total of 571 participants from the Advanced Glaucoma Intervention Study (AGIS) and the Collaborative Initial Glaucoma Treatment Study (CIGTS). Perimetric and tonometric data were obtained for AGIS and CIGTS trial participants and used to parameterize and validate a Kalman filter model. The Kalman filter updates knowledge about each participant's disease dynamics as additional VF tests and IOP measurements are obtained. After incorporating the most recent VF and IOP measurements, the model forecasts each participant's disease dynamics into the future and characterizes the forecasting error. To determine personalized schedules for future VF tests and IOP measurements, we developed an algorithm by combining the Kalman filter for state estimation with the predictive power of logistic regression to identify OAG progression. The algorithm was compared with 1-, 1.5-, and 2-year fixed interval schedules of obtaining VF and IOP measurements. Length of diagnostic delay in detecting OAG progression, efficiency of detecting progression, and number of VF and IOP measurements needed to assess for progression. Participants were followed in the AGIS and CIGTS trials for a mean (standard deviation) of 6.5 (2.8) years. Our forecasting model achieved a 29% increased efficiency in identifying OAG progression (P<0.0001) and detected OAG progression 57% sooner (reduced diagnostic delay) (P = 0.02) than following a fixed yearly monitoring schedule, without increasing the number of VF tests and IOP measurements required. The model performed well for patients with mild and advanced disease. The model performed significantly more testing of patients who exhibited OAG progression than nonprogressing patients (1.3 vs. 1.0 tests per year; P<0.0001). Use of dynamic and personalized testing schedules can enhance the efficiency of OAG progression detection and reduce diagnostic delay compared with yearly fixed monitoring intervals. If further validation studies confirm these findings, such algorithms may be able to greatly enhance OAG management.

Assessment methods of visual field defects of patients with glaucoma

Glaucoma is a common eye disease which may cause irreversible blindness.This ocular degenerative disease affects retinal ganglion cells (RGCs) and eventually causes optic nerve dysfunction by way of axonal loss.Patients with glaucoma may show characteristic changes of optic disc,damages of visual field and impairment of vision.Detection and evaluation of the impairment of visual field in patients with glaucoma are essential for the diagnosis and estimation of progression of this disease.Numerous techniques have been developed to detect field progression,but no standard has been widely accepted.Assessment Methods including visual field indices,glaucoma hemifield test (GHT),Advanced Glaucoma Intervention Study (AGIS),Early Manifest Glaucoma Trial (EMGT),Collaborative Initial Glaucoma Treatment Study(CIGTS),as well as the strength and limitation of each method were reviewed in this article in order to find out suitable ways to evaluate visual field defects in patients with glaucoma in clinical works and researches. Key words: Glaucoma; Visual field defect; Assessment

Improving predictive models of glaucoma severity by incorporating quality indicators

In this paper we present an evaluation of the role of reliability indicators in glaucoma severity prediction. In particular, we investigate whether it is possible to extract useful information from tests that would be normally discarded because they are considered unreliable. We set up a predictive modelling framework to predict glaucoma severity from visual field (VF) tests sensitivities in different reliability scenarios. Three quality indicators were considered in this study: false positives rate, false negatives rate and fixation losses. Glaucoma severity was evaluated by considering a 3-levels version of the Advanced Glaucoma Intervention Study scoring metric. A bootstrapping and class balancing technique was designed to overcome problems related to small sample size and unbalanced classes. As a classification model we selected Naïve Bayes. We also evaluated Bayesian networks to understand the relationships between the different anatomical sectors on the VF map. The methods were tested on a data set of 28,778 VF tests collected at Moorfields Eye Hospital between 1986 and 2010. Applying Friedman test followed by the post hoc Tukey's honestly significant difference test, we observed that the classifiers trained on any kind of test, regardless of its reliability, showed comparable performance with respect to the classifier trained only considering totally reliable tests (p-value>0.01). Moreover, we showed that different quality indicators gave different effects on prediction results. Training classifiers using tests that exceeded the fixation losses threshold did not have a deteriorating impact on classification results (p-value>0.01). On the contrary, using only tests that fail to comply with the constraint on false negatives significantly decreased the accuracy of the results (p-value<0.01). Meaningful patterns related to glaucoma evolution were also extracted. Results showed that classification modelling is not negatively affected by the inclusion of less reliable tests in the training process. This means that less reliable tests do not subtract useful information from a model trained using only completely reliable data. Future work will be devoted to exploring new quantitative thresholds to ensure high quality testing and low re-test rates. This could assist doctors in tuning patient follow-up and therapeutic plans, possibly slowing down disease progression.

Medikamentöse Glaukomtherapie

The prospective multicenter randomized controlled clinical trials (RCTs) Ocular Hypertension Glaucoma Treatment Study (OHTS), Early Manifest Glaucoma Trial (EMGT), Advanced Glaucoma Intervention Study (AGIS), Collaborative Initial Glaucoma Treatment Study (CITGS) and Collaborative Normal Tension Glaucoma Study (CNGTS) are often named as landmarks for glaucoma management as the results of these studies provided the evidence for numerous therapeutic decisions in clinical practice. The studies confirmed the consensus that reduction of intraocular pressure reduces the risk of glaucoma progression covering the whole spectrum of glaucoma from ocular hypertension to advanced glaucoma. Furthermore, the identification of new risk factors allows a higher precision of assessment of the risk of progression. The RCTs achieved the main goal of high level of evidence, thus making progress in the understanding of glaucoma and its treatment and bridging consensus-based and evidence-based decisions. However, the implementation of the results into clinical practice needs adequate and accurate interpretation of the results.

A modified glaucoma staging system based on visual field index

To describe a modified glaucoma staging system (Modified GSS) based on the visual field index (VFI) and evaluate the performance of the Modified GSS compared with the Bascom Palmer GSS and Enhanced GSS. A total of 549 eyes of 549 patients were studied retrospectively. The Modified GSS was used to classify the glaucomatous visual field defects into stage 0 to 5 based on the VFI. The cutoff values for each stage were derived from VFI that were equivalent to mean deviations of -6, -12, -20, and -25 dB by receiver operating characteristic analysis. The staging performances, based on each of three GSSs, were compared with both the Advanced Glaucoma Intervention Study (AGIS) and Collaborative Initial Glaucoma Treatment Study (CIGTS) scores. The VFI cutoff values calculated for each stage were 81.5, 62.5, 42.5, and 22.5%, respectively. The correlation coefficient of Modified GSS was greater than that of Bascom Palmer GSS (p < 0.001), and correlation coefficients of Modified GSS and Enhanced GSS were equivalent. However, Enhanced GSS tended to classify moderate to severe AGIS and CIGTS scores into higher stages (p < 0.001). The Modified GSS is easy to use and accurate, and the staging performance is either equal or superior to existing GSSs.

Determinants of severity at presentation among young patients with early onset glaucoma

Aim:The aim of this study was to evaluate the clinical, socio-economic, and demographic factors associated with the severity at presentation among juvenile primary open angle glaucoma (JOAG) patients.Materials and Methods:Age at diagnosis, family history, baseline intraocular pressure (IOP), access to health-care, socio-economic status, and glaucoma awareness among 80 unrelated JOAG patients presenting between 10 years and 40 years of age were analyzed for their association with the severity at presentation. Severity at presentation was graded based on worse eye visual field using the advanced glaucoma intervention study score and on binocular visual field defects at presentation.Results:Patients with a positive family history presented 4 years earlier (P = 0.045, confidence interval [CI]: 0.09-8.8) compared to those without a family history. Lower socio-economic status (Odds ratio [OR] 5.7, P = 0.01, CI: 1.5-22), and higher baseline IOP (OR 7, P = 0.003, CI: 1.9-26) were associated with severe glaucomatous visual field defect at presentation. A negative family history was associated with a 10 times likelihood of presenting with a severe glaucomatous field defect (OR 0.1, P = 0.007, CI: 0-0.5).Conclusions:Clinical, socio-economic, and demographic factors are contributory to the severity at presentation among young patients with early onset glaucoma. Presence of a family history is associated with an earlier presentation among these patients and a reduced risk of the severe presentation.

Risk Factors for Visual Field Progression in the Groningen Longitudinal Glaucoma Study

To identify risk factors for visual field progression in glaucoma and to compare different statistical approaches with this risk factor analysis. We included 221 eyes of 221 patients. Progression was analyzed using Nonparametric Progression Analysis applied to Humphrey Field Analyzer data. Risk factors were analyzed using the statistical approaches from the Advanced Glaucoma Intervention Study, the Early Manifest Glaucoma Trial, and the Canadian Glaucoma Study. Four intraocular pressure (IOP) variables (baseline IOP, mean IOP during follow-up, IOP fluctuation, and pretreatment IOP) and 8 other risk factors were investigated. On average, 7.1 reliable fields were available after a mean follow-up of 5.3 years; 89 eyes progressed. With the Advanced Glaucoma Intervention Study approach, age [odds ratio (OR) 1.03/y; 95% confidence interval (CI), 1.00-1.06; P = 0.044] predicted progression. With an additional stepwise selection procedure, mean IOP during follow-up (1.16 per mm Hg; 1.05-1.29; P=0.003),baseline HFA mean deviation (MD; 2.72 for worse versus better than --6 dB; 1.50-4.95; P=0.001) and age (1.03; 1.01-1.06;P=0.010) predicted progression [corrected]. With the Early Manifest Glaucoma Trial approach, baseline IOP [hazard ratio (HR) 1.07; 95% CI, 1.02-1.11; P = 0.010], baseline Frequency Doubling Perimeter MD (HR = 1.75; 95% CI, 1.14-2.70; P = 0.013), and age (HR = 1.03; 95% CI, 1.01-1.05; P = 0.006) predicted progression. Finally, with the Canadian Glaucoma Study approach, baseline IOP (HR = 1.07; 95% CI, 1.02-1.11; P = 0.010), baseline Frequency Doubling Perimeter MD (HR = 1.75; 95% CI, 1.14-2.70; P = 0.013), and age (HR = 1.03; 95% CI, 1.01-1.05; P = 0.006) predicted progression. IOP, disease stage, and age seemed to be robust independent risk factors for visual field progression in glaucoma. The IOP variable that was significant depended on the statistical approach applied.

The Glaucoma Guidelines of the Swedish Ophthalmological Society

The Glaucoma Guidelines of the Swedish Ophthalmological Society

Comparison of Visual Field Severity Classification Systems for Glaucoma

To compare categorical severity classification systems for glaucoma. This cross-sectional study included 1,921 eyes (49.5% right eye) from 1,137 participants from the Diagnostic Innovations in Glaucoma Study and African Descent and Glaucoma Evaluation Study. Standard automated perimetry fields were classified using the: (1) Advanced Glaucoma Intervention Study scoring system (AGIS), (2) Glaucoma Severity Staging system (GSS), and (3) Enhanced Glaucoma Severity Staging system (eGSS). Systems were characterized using the following continuous measures of severity: mean deviation, pattern standard deviation, and visual field index. Classifications between systems and with optic disc stereophotograph assessment were compared (κ) and some stages were consolidated to evaluate severity classification across systems (Wilcoxon test). Mean deviation, pattern standard deviation, and visual field index were significantly different between GSS and AGIS, and GSS and eGSS in normal and abnormal fields (P<0.005). Agreement between AGIS and eGSS was substantial (κ=0.715±0.012); agreement between GSS and eGSS (κ=0.559±0.014) and AGIS (κ=0.519±0.016) was moderate. eGSS tended to stage abnormal fields most severely followed by GSS and then AGIS (P<0.001). The presence of glaucomatous optic neuropathy increases with staging severity for all systems. However, different systems led to different severity staging. Of the systems examined in this study, eGSS may be the better choice for its ease of use for both clinicians and researchers.

Pointwise Rates of Visual Field Progression Cluster according to Retinal Nerve Fiber Layer Bundles

To explore whether pointwise rates of visual field progression group together in patterns consistent with retinal nerve fiber layer (RNFL) bundles. Three hundred eighty-nine eyes of 309 patients from the Advanced Glaucoma Intervention Study with ≥6 years of follow-up and ≥12 reliable visual field exams were selected. Linear and exponential regression models were used to estimate pointwise rates of change over time. Clustering of pointwise rates of progression was investigated with hierarchical cluster analysis using Pearson's correlation coefficients as distance measure and an average linkage scheme for building the hierarchy with cutoff value of r > 0.7. The average mean deviation (±SD) was -10.9 (±5.4). The average (±SD) follow-up time and number of visual field exams were 8.1 (±1.1) years and 15.7 (±3.0), respectively. Pointwise rates of progression across the visual field grouped into clusters consistent with anatomic patterns of RNFL bundles with both linear (10 clusters) and exponential (six clusters) regression models. One hundred forty-four (37%) eyes progressed according to the two-omitting pointwise linear regression model. ointwise rates of change in glaucoma patients cluster into regions consistent with RNFL bundle patterns. This finding validates the clinical significance of such pointwise rates. The correlations among pointwise rates of change can be used for spatial filtering purposes, facilitating detection or prediction of glaucoma progression.

The Development of a Decision Analytic Model of Changes in Mean Deviation in People with Glaucoma: The COA Model

To create and validate a statistical model predicting progression of primary open-angle glaucoma (POAG) assessed by loss of visual field as measured in mean deviation (MD) using 3 landmark studies of glaucoma progression and treatment. A Markov decision analytic model using patient level data described longitudinal MD changes over 7 years. Patient-level data from the Collaborative Initial Glaucoma Treatment Study (n = 607), the Ocular Hypertension Treatment Study (OHTS; n = 148; only those who developed POAG in the first 5 years of OHTS) and Advanced Glaucoma Intervention Study (n = 591), the COA model. We developed a Markov model with transition matrices stratified by current MD, age, race, and intraocular pressure categories and used a microsimulation approach to estimate change in MD over 7 years. Internal validation compared model prediction for 7 years to actual MD for COA participants. External validation used a cohort of glaucoma patients drawn from university clinical practices. Change in visual field as measured in MD in decibels (dB). Regressing the actual MD against the predicted produced an R(2) of 0.68 for the right eye and 0.63 for the left. The model predicted ending MD for right eyes of 65% of participants and for 63% of left eyes within 3 dB of actual results at 7 years. In external validation the model had an R(2) of 0.79 in the right eye and 0.77 in the left at 5 years. The COA model is a validated tool for clinicians, patients, and health policy makers seeking to understand longitudinal changes in MD in people with glaucoma.

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

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

Intraocular pressure reduction in normal-tension glaucoma patients in South Korea

To evaluate the potential benefit of intraocular pressure (IOP) reduction in normal-tension glaucoma (NTG) patients in South Korea. A retrospective, multi-center analysis of Korean NTG patients with 5-years follow-up, typical glaucomatous optic disc and/or visual field changes and no recorded IOP >21mmHg. Progression was identified by Advanced Glaucoma Intervention Study visual field scoring. There were 90 (42%) progressed patients and 127 (58%) stable patients included in the study. Mean IOP measured higher in the progressed (14.3±2.2mmHg) than stable patients (14.0±1.9mmHg), but was not statistically different between the groups (P=0.29). The mean IOP that best discriminated stable patients was ≤15mmHg, but no statistical difference existed in the numbers of progressed versus stable patients at ≤15mmHg compared to >15mmHg (P=0.07). Multivariate regression analysis showed that the baseline number of glaucoma medicines and visual field as well as mean, peak and fluctuation of IOP were significant risk factors for glaucomatous progression (P<0.01). This study suggests that in Korean NTG patients, despite relatively similar IOPs between progressed and stable patients, and based on multivariate regression analysis, IOP may be a risk factor for glaucomatous progression.

Intraocular Pressure: Modulation as Treatment for Glaucoma

To review the role of intervisit intraocular pressure (IOP) fluctuation as an independent risk factor for glaucoma. Perspective after literature review. Analysis of pertinent publications in the peer-reviewed literature. Disparate findings regarding the role of intervisit IOP variation have been published. IOP variation was a significant risk factor in the Advanced Glaucoma Intervention Study (AGIS), the Collaborative Initial Glaucoma Treatment Study, and other smaller studies. These studies have in common low IOPs (often after surgery) and moderately advanced disease. In the AGIS, when patients were stratified by mean IOP, only those patients with low IOPs showed the detrimental effects of IOP variation. IOP variation was not a significant risk factor in the Early Manifest Glaucoma Treatment Trial, and in 2 separate studies of ocular hypertensives. These studies have in common generally higher IOPs and an earlier stage of glaucoma (or no glaucoma at all). We believe these results are complementary rather than contradictory: existing data suggest that the effects of IOP variation depend on the characteristics of the patient, the baseline IOP, their stage of damage, the type of glaucoma, and other as-yet unknown factors. Practitioners should consider whether patients who are progressing at low mean IOP may benefit from having IOP variation reduced. Single elevated measures of IOP may not be an anomaly or may not be related to compliance, but may identify patients who are at high risk for progressive glaucomatous damage, and thus should be monitored more carefully and potentially treated more aggressively.

Influence of Visual Field Testing Frequency on Detection of Glaucoma Progression With Trend Analyses

To explore whether increased frequency of visual field testing leads to earlier detection of glaucoma progression with trend analyses. The visual fields of 468 eyes (381 patients) from the Advanced Glaucoma Intervention Study with 10 or more reliable visual field tests and 3 or more years of follow-up were studied. Starting at year 1, every other visual field examination was deleted to create a low-frequency data set, and the original group was kept as the high-frequency data set. The proportion of progressing eyes and the time to progression were compared between the 2 data sets with global and pointwise linear regression criteria. The median number of visual field examinations was 20 and 12 for the high- and low-frequency data sets, respectively. Based on primary mean deviation criteria, 204 eyes (43.6%) in the high-frequency data set and 160 eyes (34.2%) in the low-frequency data set progressed (P<.001), whereas 185 eyes (39.5%) in the high-frequency data set and 167 eyes (35.7%) in the low-frequency data set progressed according to pointwise linear regression (P=.02). The high-frequency data set was more likely to detect progression with mean deviation (hazard ratio [HR], 1.69 [95% confidence interval {CI}, 1.36-2.10]) or pointwise linear regression criteria (HR, 1.52 [95% CI, 1.21-1.90]). A similar number of improving eyes were detected with mean deviation criteria (HR, 0.95 [95% CI, 0.58-1.60]), but pointwise linear regression criteria were more likely to detect improvement in the high-frequency data set (HR, 2.27 [95% CI, 1.43-3.62]). The results did not significantly change after censoring data at 5 years. Increasing the frequency of visual field testing leads to earlier detection of glaucoma progression, especially with global trend analyses. This finding has significant implications for the care of patients with glaucoma.

Blindness and Long-Term Progression of Visual Field Defects in Chinese Patients With Primary Angle-Closure Glaucoma

To investigate the long-term rates of blindness and visual field (VF) progression in treated primary angle-closure glaucoma (PACG) patients. Retrospective observational case series. PACG patients with ≥10 years of follow-up were analyzed. All VFs (static automated perimetry, central 24-2 threshold test) performed were reviewed and reliable VFs (fixation losses <20%, false positives and false negatives <33%) were scored using the Advanced Glaucoma Intervention Study (AGIS) system. Progression of a VF defect was defined as a change of ≥4 from baseline on 2 consecutive VF tests. From the 137 eyes of 87 patients with PACG with ≥10 years of follow-up identified, 6% and 30.1% were blind based on initial visual acuity (VA) and VF criteria respectively and 12.0% had an initial AGIS score of 20; these were excluded. Eighty-three eyes from 57 patients (all Chinese, mean age 59.9 ± 8.2 years, 67.5% female) were analyzed. The mean AGIS score was 5.14 ± 4.37 at baseline. VF deterioration was detected in 27 eyes (32.5%) of 21 patients, with 4.8% and 7.2% of eyes progressing to blindness based on VA and VF criteria respectively. On Cox regression, eyes with VF progression had higher mean overall IOP (P < .001), and higher prevalence of previous acute angle closure (AAC, P = .008). Over 10 years, a third of PACG patients were found to have VF progression, with 7% progressing to blindness while on treatment. Eyes with higher mean overall IOP and a history of previous AAC were more likely to have VF progression.

The unique problem of glaucoma: Under-diagnosis and over-treatment

The unique problem of glaucoma: Under-diagnosis and over-treatment

Agreement of visual field interpretation among glaucoma specialists and comprehensive ophthalmologists: comparison of time and methods

AimsTo evaluate interobserver agreement and interpretation time for three clinically available formats of visual field presentation: serial Humphrey visual field (HVF), STATPAC2 and PROGRESSOR.Methods40 field series from the Advanced Glaucoma...

Corneal Hysteresis and Visual Field Asymmetry in Open Angle Glaucoma

To investigate the association between corneal biomechanical parameters and asymmetric primary open angle glaucoma (POAG) using the Ocular Response Analyzer (ORA). In a prospective cross-sectional study, ORA parameters were measured in 117 POAG patients with asymmetric visual fields (VF). The asymmetry in VF was defined as a five point difference between the eyes using the Advanced Glaucoma Intervention Study (AGIS) scoring system. Subjects with previous intraocular or refractive surgery, ocular comorbidities and diabetes were excluded. In worse eyes, mean AGIS scores were significantly higher (8.1 ± 4.3 vs. 1.0 ± 1.6; P < 0.001) and mean corneal hysteresis (CH) was significantly lower (8.2 ± 1.9 vs. 8.9 ± 1.9 mm Hg; P < 0.001). Median ORA-corrected intraocular pressure was higher in the worse eyes (IOP(cc), 17.4 mm Hg vs. 16.9 mm Hg; P < 0.001). Worse eyes had a slightly lower mean corneal resistance factor (P = 0.04) and more myopic mean spherical equivalent (P = 0.02). No difference was seen in the central corneal thickness (CCT; P = 0.63) and Goldmann applanation tonometry (GAT; P = 0.32). On multivariate analysis, only CH retained an association with the worse eye (odds ratio, 25.9; 95% confidence interval, 10.1-66.5). ROC curves showed that only CH and IOP(cc) had a discriminative ability for the eye with worse VF (AUC, 0.82 and 0.70, respectively). Asymmetric POAG was associated with asymmetry in ORA parameters but not in CCT and GAT. Lower CH was associated with worse eyes independently of its effect on IOP measurement and had the best discriminability for the eye with the worse VF.