Early Manifest Glaucoma Trial Criteria Research Articles

Association Between Optic Disc Perfusion Determined by Swept-Source Optical Coherence Tomography Angiography and Visual Field Progression in Glaucoma.

Reduced optic disc vessel density determined by swept-source optical coherence tomography angiography (SS-OCTA) was associated with visual field (VF) deterioration in glaucomatous eyes, which suggested that this parameter can be a potential biomarker that correlates well with functional deterioration. The purpose of this study was to identify the association between optic disc perfusion evaluated by SS-OCTA and VF progression in primary open angle glaucoma (POAG) eyes. A total of 266 POAG eyes of 266 patients (5.4y of mean follow-up) were included. Optic nerve head SS-OCTA was performed to evaluate the optic disc vessel density (dVD), parapapillary choroidal vessel density (pcVD), choroidal microvascular dropout (cMvD), and optic disc microvascular dropout (dMvD). VF progression was defined using Early Manifest Glaucoma Trial criteria. Factors associated with VF worsening were assessed by Cox proportional hazard analysis. Eighty (30.1%) out of the 266 POAG eyes showed VF progression. The progression group showed a significantly higher proportion of disc hemorrhage, cMvD, and dMvD but lower dVD and pcVD than the stable group (all P <0.05). Considering the strong association between the parameters [dMvD vs. dVD ( r = -0.757, P =0.010], cMvD vs. pcVD ( r = -0.745, P =0.012), dMvD vs. cMvD ( r = 0.802, P <0.001], dVD vs. pcVD ( r = 0.862, P <0.001), CMvD vs. dVD ( r = -0.698, P =0.031), and dMvD vs. pcVD ( r = -0.688, P =0.034)], 6 models with different combinations of covariates compensating for multicollinearity were developed. Younger age, presence of disc hemorrhage, and lower dVD were consistently associated with progression in all models that included these parameters. Optic disc perfusion, represented as dVD, may be a useful biomarker that correlates well with functional deterioration in POAG eyes.

Morning Blood Pressure Surge and Glaucomatous Visual Field Progression in Normal-Tension Glaucoma Patients With Systemic Hypertension

To investigate the impact of a morning blood pressure surge (MBPS) at baseline on subsequent visual field (VF) progression in hypertensive, normal-tension glaucoma (NTG) patients receiving oral anti-hypertensive treatment. Retrospective cohort study. A total of 127 eyes from 127 newly diagnosed NTG patients treated for systemic hypertension and followed up for at least 2 years were analyzed. All patients underwent baseline 24-hour ambulatory blood pressure monitoring (ABPM) and at least 5 serial VF examinations during the follow-up period. VF progression was defined according to the Early Manifest Glaucoma Trial criteria. The associations of VF progression with 24-hour ABPM-based blood pressure (BP) parameters (including MBPS) and other clinical variables were analyzed using Cox regression analyses. Kaplan-Meier survival analysis was used to compare VF survival estimates in patients with and without MBPS. VF progression was detected in 38 eyes (29.9%) over a 5.2-year mean follow-up. In the multivariate Cox regression model, a greater MBPS (hazard ratio [HR]=1.033; P=.024) and lower nighttime mean arterial pressure (MAP) trough (HR=0.965; P=.031) at baseline were significant independent predictors of subsequent VF progression. The likelihood of VF progression was significantly greater in patients with higher MBPS (P=.021) at baseline according to Kaplan-Meier survival analysis. An increased MBPS at baseline is a significant independent predictor of subsequent VF progression in NTG patients with systemic hypertension. This may be another relevant BP parameter associated with VF progression in hypertensive NTG patients receiving oral anti-hypertensive treatment.

Population-based associations between progression of normal-tension glaucoma and Yang-deficient constitution among Chinese persons

PurposeTo explore the association between constitution types as defined by traditional Chinese medicine (TCM) and risk for normal-tension glaucoma (NTG).DesignPopulation-based cohort study.MethodsPersons were identified in a population cohort aged ≥30...

Baseline Choroidal Microvasculature Dropout as a Predictor of Subsequent Visual Field Progression in Open-angle Glaucoma.

Choroidal microvasculature dropout (CMvD) is an independent predictor for overall and central visual field (VF) progression in open-angle glaucoma (OAG) eyes. The purpose of this study was to investigate the impact of CMvD identified by optical coherence tomography angiography (OCT-A) at baseline on subsequent VF progression in eyes with OAG. This retrospective observational study included 80 OAG eyes with CMvD [CMvD(+)] and without CMvD [(CMvD(-)] at baseline [40 of each matched for both age (10 y and below) and baseline VF severity (≤1 dB)]. The patients were followed regularly at 6-month intervals. VF progression was defined according to the Early Manifest Glaucoma Trial criteria. Associations of overall VF progression with baseline clinical factors, including the presence of CMvD and other variables, were analyzed by logistic regression with a generalized estimating equation in the entire OAG cohort. Linear mixed models were used to determine the differences in visual field mean sensitivity (VFMS) between the CMvD(+) and CMvD(-) groups globally and regionally at each follow-up point. During a mean follow-up of 35.91±2.51 months, a significant difference was evident in the VF progression rate between the CMvD(-) and CMvD(+) groups (22.5% vs. 70%, P<0.001). CMvD at baseline and a higher visit-to-visit intraocular pressure fluctuation were significant predictors of VF progression. The VFMS differed significantly between the 2 groups at the central and superior central VF regions after 2 years of follow-up. The presence of CMvD at baseline is an independent predictor of subsequent VF progression. CMvD(+) eyes show a faster rate of VFMS loss at the central and superior central VF regions.

Wide-field Trend-based Progression Analysis of Combined Retinal Nerve Fiber Layer and Ganglion Cell Inner Plexiform Layer Thickness: A New Paradigm to Improve Glaucoma Progression Detection

Evaluation of glaucoma progression with OCT has been centered on the analysis of progressive retinal nerve fiber layer (RNFL) thinning over the parapapillary region and/or progressive ganglion cell inner plexiform layer (GCIPL) thinning over the macula. We investigated (1) whether combining the RNFL and GCIPL as a single layer (i.e., RNFL-GCIPL) for wide-field progression analysis outperforms wide-field progression analysis of the RNFL or the GCIPL, and (2) whether eyes with progressive RNFL-GCIPL thinning are at risk of visual field (VF) progression. Prospective, longitudinal study. A total of 440 eyes from 236 glaucoma patients; 98 eyes from 49 healthy individuals. OCT RNFL/GCIPL/RNFL-GCIPL thickness and VF measurements were obtained at ∼4-month intervals for ≥3 years. Progressive changes of the RNFL/GCIPL/RNFL-GCIPL thicknesses were analyzed over a wide field (12×9 mm2) covering the parapapillary region and the macula with trend-based progression analysis (TPA) controlled at a false discovery rate of 5%. VF progression was determined by the Early Manifest Glaucoma Trial criteria. Proportions of eyes with progressive RNFL/GCIPL/RNFL-GCIPL thinning; hazard ratios (HRs) for development of VF progression. More eyes showed progressive RNFL-GCIPL thinning (127 eyes; 28.9%, 95% confidence interval [CI]: 23.9%-33.8%) than progressive RNFL thinning (74 eyes; 16.8%, 95% CI: 13.1%-20.6%) and progressive GCIPL thinning (26 eyes; 5.9%, 95% CI: 3.7%-8.1%) in the glaucoma group over the study follow-up. Progressive RNFL-GCIPL thinning was almost always detected before or simultaneously with progressive RNFL thinning or progressive GCIPL thinning. The specificity of TPA (estimated from the healthy group) for detection of progressive RNFL-GCIPL thinning, progressive RNFL thinning, and progressive GCIPL thinning was 83.7% (95% CI: 74.9%-92.4%), 94.9% (95% CI: 90.6%-99.2%), and 96.9% (95% CI: 93.5%-100.0%), respectively. Eyes with progressive RNFL-GCIPL thinning had a higher risk to develop possible (HR: 2.4, 95% CI: 1.2-5.0) or likely (HR: 4.6, 95% CI: 1.5-14.0) VF progression, with adjustment of covariates, compared with eyes without progressive RNFL-GCIPL thinning. Progression analysis of RNFL-GCIPL thickness reveals a significant portion of progressing eyes that neither progression analysis of RNFL thickness nor GCIPL thickness would identify. Wide-field progression analysis of RNFL-GCIPL thickness is effective to inform the risk of VF progression in glaucoma patients.

Impact of Posterior Sclera on Glaucoma Progression in Treated Myopic Normal-Tension Glaucoma Using Reconstructed Optical Coherence Tomographic Images.

To investigate factors associated with visual field (VF) progression in treated myopic normal-tension glaucoma (NTG) using a novel posterior sclera reconstruction method involving swept-source optical coherence tomography (OCT). Fifty-six myopic patients on ocular hypotensive therapy with the diagnose NTG had five or more VF tests during a period of 72.63 ± 20.46 months in clinical follow-up. Glaucomatous VF progression was decided by the standards of Early Manifest Glaucoma Trial criteria. Coronally reconstructed OCT images were used to obtain the position of the deepest point of the eye (DPE), and parameterized the distance (Disc-DPE distance), depth (Disc-DPE depth) and angle (Disc-DPE angle) of the posterior sclera. The Cox proportional hazards model and Kaplan-Meier curves were used to determine the risk factors for VF progression. Among 56 eyes, 28 showed VF progression. Eyes with progression had significantly different distance, depth, and angle of the DPE position (P = 0.049, P = 0.032, and P = 0.006, respectively). A multivariate Cox proportional hazard model revealed that the vertical tilt angle (hazard ratio [HR] 0.835, P = 0.026) and the DPE positioned temporal to fovea (HR 4.314, P = 0.001) were associated with VF progression. Among eyes with DPE positioned temporal to fovea, in addition to percentage reduction in IOP from baseline (HR 0.915, P = 0.012), shorter axial length (HR 0.542, P = 0.044) was found to be associated with VF progression. Eyes with a particular posterior sclera structure are at increased risk for glaucoma progression in treated myopic NTG patients. This finding highlights the significance of investigating posterior sclera structure and its relevance to initiate or augment treatment for myopic glaucoma patients.

Baseline Systolic versus Diastolic Blood Pressure Dip and Subsequent Visual Field Progression in Normal-Tension Glaucoma

To investigate the impact of systolic and diastolic blood pressure (DBP) dip at baseline on subsequent visual field (VF) progression in eyes with normal-tension glaucoma (NTG). Prospective cohort study. This study included 119 eyes of 119 newly diagnosed NTG patients followed up for at least 2 years (average, 40.4±16.9 months). All participants underwent baseline 24-hour ambulatory blood pressure (BP) monitoring and measurements of intraocular pressure (IOP) and at least 5 serial VF examinations. Participants were followed up as outpatients at 4- to 6-month intervals. Visual field progression was defined according to Early Manifest Glaucoma Trial criteria. The associations of VF progression with systolic BP (SBP) and DBP measured during the day and at night and other clinical variables were analyzed. Factors associated with VF progression over time. During follow-up, 41 eyes (34%) showed VF progression. In the multivariate Cox regression model, lower nighttime trough DBP (hazard ratio, 0.953; P= 0.023) and greater nighttime DBP dip area (time multiplied by nighttime DBP > 10 mmHg less than mean daytime DBP; hazard ratio, 1.017; P= 0.003) at baseline were significant predictors of subsequent VF progression. None of the SBP parameters was associated with VF progression. Nocturnal DBP dip showed a greater association with VF progression than SBP dip. Nocturnal trough DBP and DBP dip area at baseline are significant predictors of subsequent VF progression in NTG. Nocturnal DBP dip may be more relevant to future VF progression than SBP dip in NTG eyes.

Patterns of Progressive Ganglion Cell–Inner Plexiform Layer Thinning in Glaucoma Detected by OCT

To investigate the spatial characteristics and patterns of progressive macular ganglion cell-inner plexiform layer (GCIPL) thinning in glaucomatous eyes assessed by OCT Guided Progression Analysis (GPA). Longitudinal, retrospective, observational study. Two hundred ninety-two eyes of 192 patients with primary open-angle glaucoma with a mean follow-up of 6.0 years (range, 3.2-8.1 years) were included. Macular GCIPL imaging and visual field (VF) examination were performed at 6-month intervals for 3 years or more. Progressive GCIPL thinning was evaluated by a Cirrus HD-OCT (Carl Zeiss Meditec, Dublin, CA) GPA device. Spatial characteristics of progressive GCIPL thinning were assessed by the GCIPL thickness change map. The pattern of progressive GCIPL thinning was evaluated by comparing the baseline GCIPL thickness deviation map and the final GCIPL thickness change map. Visual field progression was determined by Early Manifest Glaucoma Trial criteria and linear regression of the VF index. Spatial characteristics and patterns of progressive GCIPL thinning. Seventy-two eyes of 62 participants (24.7% [72/292]) showed progressive GCIPL thinning in the GCIPL thickness change map. Progressive GCIPL thinning was detected most frequently (25.0%) at 2.08 mm from the fovea, and it extended in an arcuate shape in the inferotemporal region (250°-339°). Compared with the baseline GCIPL defects, the progressive GCIPL thinning extended toward the fovea and optic disc. The most common pattern of progressive GCIPL thinning was widening of GCIPL defects (42 eyes [58.3%]), followed by deepening of GCIPL defects (19 eyes [26.4%]) and newly developed GCIPL defects (15 eyes [20.8%]). Visual field progression was accompanied by progressive GCIPL thinning in 41 of 72 eyes (56.9%). Progressive GCIPL thinning preceded (61.0% [25/41]) or occurred concomitantly with (21.9% [9/41]) VF progression. The use of OCT GPA maps offers an effective approach to evaluate the topographic patterns of progressive GCIPL thinning in glaucomatous eyes. Progression of GCIPL thinning occurred before apparent progression on standard automated perimetry in most glaucomatous eyes. Understanding specific patterns and sequences of macular damage may provide important insights in the monitoring of glaucomatous progression.

Integrating Macular Ganglion Cell Inner Plexiform Layer and Parapapillary Retinal Nerve Fiber Layer Measurements to Detect Glaucoma Progression

To investigate the temporal relationship among progressive macular ganglion cell inner plexiform layer (GCIPL) thinning, progressive parapapillary retinal nerve fiber layer (RNFL) thinning, and visual field (VF) progression in patients with primary open-angle glaucoma (POAG). Prospective study. One hundred thirty-six POAG patients (231 eyes) followed up for ≥5 years. OCT imaging of the macular GCIPL and parapapillary RNFL and perimetry were performed at ∼ 4-month intervals. Progressive GCIPL and RNFL thinning were determined by Guided Progression Analysis (GPA) of serial GCIPL and RNFL thickness maps. The specificities of GPA were calculated from the proportions of eyes with progressive GCIPL or RNFL thinning in 67 eyes of 36 healthy individuals followed up for ≥5 years. Visual field progression (likely or possible) was determined by the Early Manifest Glaucoma Trial criteria. Hazard ratios for VF progression, progressive RNFL thinning, and progressive GCIPL thinning, as determined by time-varying Cox models. GPA detected 57 eyes (24.7%) with progressive GCIPL thinning and 66 eyes (28.6%) with progressive RNFL thinning at a specificity of 95.5% and 91.0%, respectively. Thirty-five eyes (15.2%) demonstrated progressive RNFL and GCIPL thinning, whereas 53 eyes (22.9%) demonstrated progressive RNFL or GCIPL thinning. Eyes with progressive GCIPL thinning had a higher risk for progressive RNFL thinning (HR, 5.27; 95% confidence interval [CI], 2.89-9.62), whereas eyes with progressive RNFL thinning were also at a higher risk for progressive GCIPL thinning (HR, 2.99; 95% CI, 1.48-6.02), after adjusting for baseline covariates. The HRs for likely and possible VF progression were 3.48 (95% CI, 1.51-8.01) and 2.74 (95% CI, 1.26-5.98), respectively, on detection of progressive GCIPL thinning and 3.66 (95% CI, 1.68-7.97) and 2.54 (95% CI, 1.23-5.21), respectively, on detection of progressive RNFL thinning after adjusting for baseline covariates. Eyes with VF progression were not at risk of progressive RNFL or GCIPL thinning (P ≥ 0.493). Progressive macular GCIPL thinning and progressive parapapillary RNFL thinning are mutually predictive. Because progressive RNFL thinning and progressive GCIPL thinning are both indicative of VF progression, integrating macular GCIPL and parapapillary RNFL measurements is relevant to facilitate early detection of disease deterioration in glaucoma patients.

Relationship between Progressive Changes in Lamina Cribrosa Depth and Deterioration of Visual Field Loss in Glaucomatous Eyes.

PurposeTo investigate the relationship between the progression of visual field (VF) loss and changes in lamina cribrosa depth (LCD) as determined by spectral-domain optical coherence tomography (SD-OCT) enhanced depth imaging in patients with primary open angle glaucoma (POAG).MethodsData from 60 POAG patients (mean follow-up, 3.5 ± 0.7 years) were included in this retrospective study. The LCD was measured in the optic disc image using SD-OCT enhanced depth imaging scanning at each visit. Change in the LCD was considered to either ‘increase’ or ‘decrease’ when the differences between baseline and the latest two consecutive follow-up visits were greater than the corresponding reproducibility coefficient value (23.08 µm, as determined in a preliminary reproducibility study). All participants were divided into three groups: increased LCD (ILCD), decreased LCD (DLCD), and no LCD change (NLCD). The Early Manifest Glaucoma Trial criteria were used to define VF deterioration. Kaplan-Meier survival analysis and Cox's proportional hazard models were performed to explore the relationship between VF progression and LCD change.ResultsOf the 60 eyes examined, 35.0% (21 eyes), 28.3% (17 eyes), and 36.7% (22 eyes) were classified as the ILCD, DLCD, and NLCD groups, respectively. Kaplan-Meier survival analysis showed a greater cumulative probability of VF progression in the ILCD group than in the NLCD (p < 0.001) or DLCD groups (p = 0.018). Increased LCD was identified as the only risk factor for VF progression in the Cox proportional hazard models (hazard ratio, 1.008; 95% confidence interval, 1.000 to 1.015; p = 0.047).ConclusionsIncreased LCD was associated with a greater possibility of VF progression. The quantitative measurement of LCD changes, determined by SD-OCT, is a potential biomarker for the prediction of VF deterioration in patients with POAG.

Impact of Rates of Change of Lamina Cribrosa and Optic Nerve Head Surface Depths on Visual Field Progression in Glaucoma.

To investigate the impact of the rates of change of anterior lamina cribrosa surface depth (ALCSD) and optic nerve head surface depth (ONHSD) on visual field (VF) progression in glaucoma. One hundred forty-six eyes of 95 glaucoma patients had optical coherence tomography ONH imaging and VF testing at approximately 4-month intervals for greater than or equal to 5 years. Anterior lamina cribrosa surface depth and ONHSD were measured with reference to (1) Bruch's membrane opening (BMO), and (2) choroid-sclera interface (CSI). The rates of change of ALCSD and ONHSD of individual eyes were measured with linear regression analysis. The hazard ratios (HRs) of the rates of change of ALCSD/ONHSD for prediction of VF progression as per Early Manifest Glaucoma Trial criteria were determined by joint longitudinal and survival models. Using the BMO reference, 23.3% and 28.1% of eyes showed a significant positive trend (posterior displacement), whereas 29.5% and 24.0% showed a significant negative trend (anterior displacement) of ALCSD and ONHSD, respectively. Using the CSI reference, the proportions with a significant negative trend decreased to 11.6% and 14.4%, respectively; and the proportions with a significant positive trend increased to 37.7% and 38.4%, respectively. The HRs of VF progression were 1.06 and 1.11 for each micrometer per year increase in the rates of change of ALCSDBMO and ONHSDBMO, respectively; and 1.07 and 1.09 for each micrometer per year increase in the rates of change of ALCSDCSI and ONHSDCSI, respectively. Identifying fast progressors of posterior ALCS/ONHS displacement is relevant to the management of glaucoma patients as they have a higher risk of VF progression.

Trend-Based Progression Analysis for Examination of the Topography of Rates of Retinal Nerve Fiber Layer Thinning in Glaucoma

Measurement of the rates of retinal nerve fiber layer (RNFL) thinning has consisted primarily of the circumpapillary RNFL profile. This study reports the rates of RNFL thinning over the 6 × 6 mm2 RNFL thickness map and their application for indication of visual field (VF) worsening in patients with glaucoma. To investigate the association between the rates of RNFL thinning and the risk of VF worsening in patients with glaucoma. This prospective study included 117 eyes of 89 Chinese patients with primary open-angle glaucoma followed up at approximate 4-month intervals for 5 or more years between July 1, 2007, and October 30, 2015, with progressive RNFL thinning detected by optical coherence tomography trend-based progression analysis (TPA). The mean and the peak rates of RNFL thinning and the area of progressive RNFL thinning were measured by the rates of change of RNFL thickness map. Visual field worsening was determined by the Early Manifest Glaucoma Trial and pointwise linear regression criteria. Hazard ratios (HRs) for indication of VF worsening determined by time-varying Weibull survival models. Of 89 patients (117 eyes) included in the study, 53 (59.6%) were men; mean (SD) age was 54.0 (13.8) years. At the time that progressive RNFL thinning was confirmed by TPA, the mean and the peak rates of RNFL thinning were 9.06 (8.05) µm/y and 4.52 (3.19) µm/y, respectively, and the area of progressive RNFL thinning was 1.54 (1.83) mm2. The inferotemporal meridians at 268° to 288° and the superotemporal meridians at 40° to 60° were the most frequent locations where progressive RNFL thinning was observed; 41.9% of the eyes had progressive RNFL thinning at these locations. After controlling for baseline covariates, the peak and the mean rates of RNFL thinning, but not the area of progressive RNFL thinning, were indicative of VF worsening. For each micrometer-per-year increase in the peak and the mean rates of RNFL thinning, the hazard ratios were 1.12 (95% CI, 1.04-1.19) for the peak rate and 1.39 (95% CI, 1.19-1.62) for the mean rate by the Early Manifest Glaucoma Trial criteria, and 1.07 (95% CI, 1.03-1.10) for the peak rate and 1.18 (95% CI, 1.09-1.28) for the mean rate by the pointwise linear regression criteria. Topographic measurement of the rates of RNFL thinning by optical coherence tomography TPA is informative for risk assessment of VF loss in glaucoma. Although progressive RNFL thinning may not necessarily be associated with VF worsening, faster rates of RNFL thinning were associated with a higher risk of subsequent decline in VF.

Optic Disc Rotation as a Clue for Predicting Visual Field Progression in Myopic Normal-Tension Glaucoma

To investigate factors associated with visual field (VF) progression in myopic normal-tension glaucoma (NTG) and to determine the relationship between optic disc rotation and VF progression. Retrospective, observational study. Ninety-two patients with myopic NTG, with VF loss confined to a single hemifield, who were followed up over a 2-year period. Systemic and ocular findings such as optic disc tilt and optic disc rotation were evaluated. The eyes with optic disc rotation accompanying a corresponding VF defect were defined as those with correspondence. Visual field progression was defined by Early Manifest Glaucoma Trial criteria. The Cox proportional hazards model was used to determine the risk factors for VF progression. Progression of VF. The mean age of subjects was 37.83±10.89 years, mean spherical equivalent refractive error was-5.51±3.37 diopters, and mean axial length was 26.18±1.79 mm. Mean follow-up duration was 55.78±30.12 months. Among 92 eyes, 37 showed VF progression. A multivariate Cox proportional hazard modelrevealed that percentage reduction in intraocular pressure (IOP) from baseline (hazard ratio [HR], 0.965; P= 0.013), optic disc hemorrhage (HR, 2.623; P= 0.019), and optic disc rotation-VF defect correspondence (HR, 0.441; P= 0.016) were associated with VF progression in myopic NTG eyes. In addition to the percentage reduction in IOP from baseline and optic disc hemorrhage, optic disc rotation-VF defect correspondence may be an important prognostic factor for patients with myopic NTG.

Risk of Visual Field Progression in Glaucoma Patients with Progressive Retinal Nerve Fiber Layer Thinning: A 5-Year Prospective Study

To investigate whether progressive retinal nerve fiber layer (RNFL) thinning is predictive of progressive visual field (VF) loss in glaucoma. Prospective study. A total of 139 primary open-angle glaucoma patients (240 eyes) followed up for ≥5 years. Retinal nerve fiber layer imaging and VF testing were performed at ∼4-month intervals. Progressive RNFL thinning was determined by event analysis (Guided Progression Analysis [GPA]) and trend analysis (Trend-based Progression Analysis [TPA]) of serial registered RNFL thickness maps. VF progression was detected according to the Early Manifest Glaucoma Trial (EMGT) ("likely progression") and pointwise linear regression (PLR) criteria (≥3 contiguous locations with sensitivity change <0 decibels [dB]/year at P < 0.01). Hazard ratios (HRs) for predicting VF progression were calculated by Cox proportional hazard modeling with progressive RNFL thinning as a time-dependent covariate. The specificity of GPA/TPA for detection of RNFL changes was determined by the proportion of eyes with significant RNFL thinning/thickening in 25 normal subjects followed weekly for 8 consecutive weeks and the proportion with significant RNFL thickening in the glaucoma group. The HRs of VF progression. A total of 65 (27.1%) and 117 eyes (48.8%) had progressive RNFL thinning based on GPA and TPA, respectively, and 30 (12.5%) and 39 eyes (16.3%) had VF progression per the EMGT and PLR criteria, respectively, during follow-up. Eyes with progressive RNFL thinning had lower VF survival estimates and a faster decline of visual field index than eyes without. Progressive RNFL thinning predicted the development of VF progression with HRs of 8.44 (95% confidence interval, 3.30-21.61) (EMGT criteria) and 5.11 (2.51-10.42) (PLR criteria) for TPA and 3.95 (1.74-8.93) (EMGT criteria) and 3.81 (1.83-7.92) (PLR criteria) for GPA after controlling for baseline covariates. The specificities of GPA and TPA were 100% (83.4%-100.0%) in the normal group and 81.7% (76.2%-86.4%) and 84.2% (78.9%-88.6%), respectively, in the glaucoma group. Progressive RNFL thinning determined by GPA and TPA is predictive of detectable functional decline in glaucoma. This finding underscores the significance of detecting progressive RNFL thinning and itsrelevance to initiate or augment treatment for glaucoma patients. Regulatory authorities may consider progressive RNFL thinning as an outcome measure in clinical trials for evaluation of glaucoma treatment.

Integrating Personalized Genomic Medicine Into Routine Clinical Care: Addressing the Social and Policy Issues of Pharmacogenomic Testing

The provision of personalized genomic medicine presents significant policy challenges, such as ensuring equitable patient access to testing, preparing clinicians to manage genomic results, justifying test reimbursement, sharing genomic information for patient care, and protecting patients against misuse of genetic information.

Retinal Nerve Fiber Layer Imaging with Spectral-domain Optical Coherence Tomography: Patterns of Retinal Nerve Fiber Layer Progression

To examine the use of the retinal nerve fiber layer (RNFL) thickness map generated by a spectral-domain optical coherence tomography (OCT) to detect RNFL progression and identify the pattern of progressive changes of RNFL defects in glaucoma. Prospective, longitudinal study. One hundred eighty-six eyes of 103 glaucoma patients. Patients were followed at 4-month intervals for ≥ 36 months for RNFL imaging and visual field examination. Both eyes were imaged by the Cirrus HD-OCT (Carl Zeiss Meditec Inc., Dublin, CA) and had visual field testing at the same visits. We defined RNFL progression by Guided Progression Analysis (Carl Zeiss Meditec) of serial RNFL thickness maps. The pattern of RNFL progression was evaluated by comparing the baseline RNFL thickness deviation map and the RNFL thickness change map. Visual field progression was defined by trend analysis of visual field index and event analysis based on the Early Manifest Glaucoma Trial criteria. The presence and the pattern of RNFL progression. A total of 2135 OCT images were reviewed. Twenty-eight eyes (15.1%) from 24 patients (23.3%) had RNFL progression detected by RNFL thickness map analysis. Three RNFL progression patterns were observed: (1) widening of RNFL defects (24 eyes, 85.7%), (2) deepening of RNFL defects (2 eyes, 7.1%, both had concomitant widening of RNFL defects), and (3) development of new RNFL defects (5 eyes, 17.9%). The inferotemporal meridian (324°-336°) 2.0 mm away from the optic disc center was the most frequent location where RNFL progression was detected. Thirteen eyes (46.4%) had concomitant visual field progression; 61.5% (n = 8) of these had RNFL progression that preceded or occurred concurrently with visual field progression. Forty-two eyes from 37 patients (22.6%) had visual field progression by trend and/or event analyses without progression in the RNFL thickness map. Analysis of serial RNFL thickness maps generated by the spectral-domain OCT facilitates the detection of RNFL progression in glaucoma.

A Comparison of Visual Field Progression Criteria of 3 Major Glaucoma Trials in Early Manifest Glaucoma Trial Patients

Three major glaucoma trials, all using the same Humphrey visual field tests, specified different criteria to define visual field progression. This article compares the performance of these criteria with a reference standard of unanimous classifications by 3 independent glaucoma experts. Longitudinal, comparative study of diagnostic criteria. Two hundred forty-five patients with manifest glaucoma in the Early Manifest Glaucoma Trial (EMGT). Visual field series of 1 eye of each of 245 EMGT patients were classified by 3 independent glaucoma specialists as definitely progressing, definitely nonprogressing, or neither. Field series that were classified in the first 2 categories by all 3 experts met the reference standards for the progressing and nonprogressing groups and were analyzed according to the progression criteria of the Advanced Glaucoma Intervention Study (AGIS), the Collaborative Initial Glaucoma Treatment Study (CIGTS), and the EMGT. Sensitivity, specificity, time to progression, and sustainability were calculated. Progression, nonprogression, sensitivity, specificity, time to progression, and sustainability. Seventy-seven field series were definitely progressing, and 95 series were definitely nonprogressing. Among progressing eyes, 45 (58%) of 77 were identified using AGIS criteria, 58 (75%) of 77 were identified with CIGTS criteria, and 74 (96%) of 77 were identified with EMGT criteria; all comparisons of sensitivities were significant, simultaneous (P<0.001), and pairwise (P<0.01). The specificity for EMGT criteria was 89%, lower (P<0.05) than that of AGIS (98%) and CIGTS (99%) criteria. Median time to progression was considerably shorter with EMGT criteria (33 months; 95% confidence interval [CI], 30-36 months) than with AGIS (66 months; 95% CI, 57-78 months) and CIGTS (55 months; 95% CI, 48-66 months) criteria. Sustainability increased with time after progression; it averaged 79%, 84%, and 81%, respectively, for AGIS, CIGTS, and EMGT criteria during the first year after the first progression and 95%, 100%, and 93% during the fourth year after progression. The EMGT criteria identified progression earlier and more often than AGIS and CIGTS criteria. Specificity was good for all criteria but was better with AGIS and CIGTS than with EMGT criteria. Sustainability was high for all 3 sets of criteria and best for CIGTS criteria and increased with time after progression.