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Detecting glaucomatous progression is an important aspect of glaucoma management. The assessment of longitudinal series of visual fields, measured using Standard Automated Perimetry (SAP), is considered the reference standard for this effort. We seek efficient techniques for determining progression from longitudinal visual fields by formulating the problem as an optimization framework, learned from a population of glaucoma data. The longitudinal data from each patient's eye were used in a convex optimization framework to find a vector that is representative of the progression direction of the sample population, as a whole. Post-hoc analysis of longitudinal visual fields across the derived vector led to optimal progression (change) detection. The proposed method was compared to recently described progression detection methods and to linear regression of instrument-defined global indices, and showed slightly higher sensitivities at the highest specificities than other methods (a clinically desirable result). The proposed approach is simpler, faster, and more efficient for detecting glaucomatous changes, compared to our previously proposed machine learning-based methods, although it provides somewhat less information. This approach has potential application in glaucoma clinics for patient monitoring and in research centers for classification of study participants., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Purpose: To analyze static visual field sensitivity with topographic models of the hill of vision (HOV), and to characterize several visual function indices derived from the HOV volume., Methods: A software application, Visual Field Modeling and Analysis (VFMA), was developed for static perimetry data visualization and analysis. Three-dimensional HOV models were generated for 16 healthy subjects and 82 retinitis pigmentosa patients. Volumetric visual function indices, which are measures of quantity and comparable regardless of perimeter test pattern, were investigated. Cross-validation, reliability, and cross-sectional analyses were performed to assess this methodology and compare the volumetric indices to conventional mean sensitivity and mean deviation. Floor effects were evaluated by computer simulation., Results: Cross-validation yielded an overall R 2 of 0.68 and index of agreement of 0.89, which were consistent among subject groups, indicating good accuracy. Volumetric and conventional indices were comparable in terms of test-retest variability and discriminability among subject groups. Simulated floor effects did not negatively impact the repeatability of any index, but large floor changes altered the discriminability for regional volumetric indices., Conclusions: VFMA is an effective tool for clinical and research analyses of static perimetry data. Topographic models of the HOV aid the visualization of field defects, and topographically derived indices quantify the magnitude and extent of visual field sensitivity., Translational Relevance: VFMA assists with the interpretation of visual field data from any perimetric device and any test location pattern. Topographic models and volumetric indices are suitable for diagnosis, monitoring of field loss, patient counseling, and endpoints in therapeutic trials.

Purpose: We compared the abilities of Stratus optical coherence tomography (OCT), Heidelberg retinal tomography (HRT) and standard automated perimetry (SAP) to detect the progression of normal tension glaucoma (NTG) in patients whose eyes displayed localized retinal nerve fiber layer (RNFL) defect enlargements., Methods: One hundred four NTG patients were selected who met the selection criteria: a localized RNFL defect visible on red-free fundus photography, a minimum of five years of follow-up, and a minimum of five reliable SAP, Stratus OCT and HRT tests. Tests which detected progression at any visit during the 5-year follow-up were identified, and patients were further classified according to the state of the glaucoma using the mean deviation (MD) of SAP. For each test, the overall rates of change were calculated for parameters that differed significantly between patients with and without NTG progression., Results: Forty-seven (45%) out of 104 eyes displayed progression that could be detected by red-free fundus photography. Progression was detected in 27 (57%) eyes using SAP, 19 (40%) eyes using OCT, and 17 (36%) eyes using HRT. In early NTG, SAP detected progression in 44% of eyes, and this increased to 70% in advanced NTG. In contrast, OCT and HRT detected progression in 50 and 7% of eyes during early NTG, but only 30 and 0% of eyes in advanced NTG, respectively. Among several parameters, the rates of change that differed significantly between patients with and without progression were the MD of SAP (p = 0.013), and the inferior RNFL thickness (p = 0.041) and average RNFL thickness (p = 0.032) determined by OCT., Conclusions: SAP had a higher detection rate of NTG progression than other tests, especially in patients with advanced glaucoma, when we defined progression as the enlargement of a localized RNFL defect. The rates of change of the MD of SAP, inferior RNFL thickness, and average RNFL thickness differed between NTG patients with and without progression.

Purpose: To evaluate and compare the ability of pointwise linear, exponential, and logistic functions, and combinations of functions, to model the longitudinal behavior of visual field (VF) series and predict future VF loss in patients with glaucoma., Methods: Visual field series from 782 eyes (572 patients) with open-angle glaucoma had greater than 6 years of follow-up and 12 VFs performed. Threshold sensitivities from the first 5 years at each location were regressed with linear, exponential, and logistic functions to estimate model parameters. A multiple-model approach applied the model with the lowest root mean square error (RMSE) at each location as the preferred model for future predictions. Predictions for each model were compared at 1, 2, 3, and 5 years after the last VF used to determine model parameters., Results: There were no clinically important differences between any of the models tested for fit; however, the logistic function had the lowest average RMSE (P < 0.001). For predictions, the exponential model consistently had the lowest average prediction RMSE for all time intervals (P < 0.001); the multiple-model approach did not perform better than the exponential model (P < 0.001)., Conclusions: While the logistic model best fit glaucomatous VF behavior over a long time period, the exponential model provided the best average predictions. A multiple-model approach for VF predictions was associated with a greater prediction error than with the best-performing single-model approach. A model's goodness of fit is not indicative of its predictive ability for measurements of glaucomatous VFs., (Copyright 2014 The Association for Research in Vision and Ophthalmology, Inc.)

Abstract: Early diagnosis of glaucoma is critical to prevent permanent structural damage and irreversible vision loss. Detection of glaucoma typically relies on examination of structural damage to the optic nerve combined with measurements of visual function. To aid the clinician in evaluation of visual function and structure, computer-based devices such as confocal scanning laser ophthalmoscopy, scanning laser polarimetry, and optical coherence tomography provide quantitative assessments of structural damage, and visual function testing includes standard automated perimetry as well as selective techniques, including short-wavelength automated perimetry and frequency-doubling technology perimetry are available. This article will review current literature on diagnostic modalities available for glaucoma with emphasis on the best evidence available in the literature to support their use in clinical practice. [Copyright &y& Elsevier]

Purpose: We compared the detection of visual field progression and its rate of change between standard automated perimetry (SAP) and Matrix frequency doubling technology perimetry (FDTP) in glaucoma., Methods: We followed prospectively 217 eyes (179 glaucoma and 38 normal eyes) for SAP and FDTP testing at 4-month intervals for ≥36 months. Pointwise linear regression analysis was performed. A test location was considered progressing when the rate of change of visual sensitivity was ≤-1 dB/y for nonedge and ≤-2 dB/y for edge locations. Three criteria were used to define progression in an eye: ≥3 adjacent nonedge test locations (conservative), any three locations (moderate), and any two locations (liberal) progressed. The rate of change of visual sensitivity was calculated with linear mixed models., Results: Of the 217 eyes, 6.1% and 3.9% progressed with the conservative criteria, 14.5% and 5.6% of eyes progressed with the moderate criteria, and 20.1% and 11.7% of eyes progressed with the liberal criteria by FDTP and SAP, respectively. Taking all test locations into consideration (total, 54 × 179 locations), FDTP detected more progressing locations (176) than SAP (103, P < 0.001). The rate of change of visual field mean deviation (MD) was significantly faster for FDTP (all with P < 0.001). No eyes showed progression in the normal group using the conservative and the moderate criteria., Conclusions: With a faster rate of change of visual sensitivity, FDTP detected more progressing eyes than SAP at a comparable level of specificity. Frequency doubling technology perimetry can provide a useful alternative to monitor glaucoma progression.

Purpose: To investigate baseline prognostic factors predicting rapid deterioration of the visual field in primary open-angle glaucoma patients., Methods: 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., Results: 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)., Conclusions: 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.

Purpose: Multifocal visual evoked potential (mfVEP) is a newly introduced method used for objective visual field assessment. Several analysis protocols have been tested to identify early visual field losses in glaucoma patients using the mfVEP technique, some were successful in detection of field defects, which were comparable to the standard automated perimetry (SAP) visual field assessment, and others were not very informative and needed more adjustment and research work. In this study we implemented a novel analysis approach and evaluated its validity and whether it could be used effectively for early detection of visual field defects in glaucoma., Methods: Three groups were tested in this study; normal controls (38 eyes), glaucoma patients (36 eyes) and glaucoma suspect patients (38 eyes). All subjects had a two standard Humphrey field analyzer (HFA) test 24-2 and a single mfVEP test undertaken in one session. Analysis of the mfVEP results was done using the new analysis protocol; the hemifield sector analysis (HSA) protocol. Analysis of the HFA was done using the standard grading system., Results: Analysis of mfVEP results showed that there was a statistically significant difference between the three groups in the mean signal to noise ratio (ANOVA test, p < 0.001 with a 95% confidence interval). The difference between superior and inferior hemispheres in all subjects were statistically significant in the glaucoma patient group in all 11 sectors (t-test, p < 0.001), partially significant in 5 / 11 (t-test, p < 0.01), and no statistical difference in most sectors of the normal group (1 / 11 sectors was significant, t-test, p < 0.9). Sensitivity and specificity of the HSA protocol in detecting glaucoma was 97% and 86%, respectively, and for glaucoma suspect patients the values were 89% and 79%, respectively., Conclusions: The new HSA protocol used in the mfVEP testing can be applied to detect glaucomatous visual field defects in both glaucoma and glaucoma suspect patients. Using this protocol can provide information about focal visual field differences across the horizontal midline, which can be utilized to differentiate between glaucoma and normal subjects. Sensitivity and specificity of the mfVEP test showed very promising results and correlated with other anatomical changes in glaucoma field loss.

Purpose: To improve the detection of glaucoma, techniques for assessing local patterns of damage and for combining structure and function were developed., Methods: Standard automated perimetry (SAP) and frequency-domain optical coherence tomography (fdOCT) data, consisting of macular retinal ganglion cell plus inner plexiform layer (mRGCPL) as well as macular and optic disc retinal nerve fiber layer (mRNFL and dRNFL) thicknesses, were collected from 52 eyes of 52 healthy controls and 156 eyes of 96 glaucoma suspects and patients. In addition to generating simple global metrics, SAP and fdOCT data were searched for contiguous clusters of abnormal points and converted to a continuous metric (pcc). The pcc metric, along with simpler methods, was used to combine the information from the SAP and fdOCT. The performance of different methods was assessed using the area under receiver operator characteristic curves (AROC scores)., Results: The pcc metric performed better than simple global measures for both the fdOCT and SAP. The best combined structure-function metric (mRGCPL&SAP pcc, AROC = 0.868 ± 0.032) was better (statistically significant) than the best metrics for independent measures of structure and function. When SAP was used as part of the inclusion and exclusion criteria, AROC scores increased for all metrics, including the best combined structure-function metric (AROC = 0.975 ± 0.014)., Conclusions: A combined structure-function metric improved the detection of glaucomatous eyes. Overall, the primary sources of value-added for glaucoma detection stem from the continuous cluster search (the pcc), the mRGCPL data, and the combination of structure and function.