African Descent And Glaucoma Evaluation Study Research Articles

Time to Glaucoma Progression Detection by Optical Coherence Tomography in Individuals of African and European Descents

To examine the time to detectable retinal nerve fiber layer thickness (RNFLT) progression by optical coherence tomography (OCT) among glaucoma patients of African descent (AD) and European descent (ED). Retrospective cohort study. AD and ED glaucoma eyes from the Diagnostic Innovations in Glaucoma Study (DIGS)/African Descent and Glaucoma Evaluation Study (ADAGES) with≥2 years/4 visits of optic nerve head RNFLT measurements were included after homogenization on age, diagnosis, and baseline visual field (VF) measurement. RNFLT variability estimates based on linear mixed-effects models were used to simulate longitudinal RNFLT data for both races. Times to trend-based RNFLT progression detection were calculated under standardized scenarios (same RNFLT baseline/thinning rates for both races) and real-world scenarios (AD and ED cohort-specific RNFLT baseline/thinning rates). We included 332 and 542 eyes (216 and 317 participants) of AD and ED, respectively. In standardized scenarios, the time to detect RNFLT progression appeared to be similar (difference, <0.2 years) for AD and ED across different assumed RNFLT thinning rates/baseline. In real-world scenarios, compared to ED, AD had a faster RNFLT thinning rate (-0.8 vs -0.6 µm/y) and thicker baseline RNFLT (84.6 vs 81.8 µm). With a faster thinning rate, the mean (SD) time to progression detection was shorter in AD (4.8 [2.0] vs ED: 5.4 [2.4] years), and the 5-year progression rate appeared to be higher (AD: 59% vs ED: 47%). Time to progression detection was similar for both races when assuming identical RNFLT baseline/thinning rates, and shorter in AD eyes under real-world simulation when AD had faster RNFLT thinning. In contrast to prior results on VF, which detected progression later in AD eyes than in ED eyes, OCT may detect progression more consistently across these races.

Associations of smoking and alcohol consumption with the development of open angle glaucoma: a retrospective cohort study

ObjectivesTo investigate the associations of alcohol consumption and smoking with the development of perimetric glaucoma in patients with suspected glaucoma.DesignA retrospective cohort study of patients suspected to have glaucoma enrolled...

Detecting Progression in Patients With Different Clinical Presentations of Primary Open-angle Glaucoma.

Précis:Glaucoma progression was more frequently identified by assessing retinal fiber layer thickness than by monitoring visual field (VF) loss for different baseline classifications in primary open-angle glaucoma.Purpose:The aim was to compare the detection of glaucoma progression by retinal nerve fiber layer thickness (RNFLT) and VF assessments for different baseline classifications of primary open-angle glaucoma.Methods:This study included 194 eyes from 194 patients with a minimum of 9 follow-up visits selected from the Diagnostic Innovation in Glaucoma Study (DIGS) and the African Descent and Glaucoma Evaluation Study (ADAGES). Each eye was classified according to baseline clinical signs: ocular hypertension (n=39), glaucomatous optic neuropathy only (n=60), glaucomatous visual field loss only (GVF, n=39) and definite glaucoma (concurrent optic disc and VF defect, n=56). We assessed progression by performing simple linear regression on global and sectorial mean deviations values generated for RNFLT (RNFLT-MD) and VF data (VF-MD). The proportion of eyes identified as progressing (positive rate) by RNFLT-MD and by VF-MD were compared within each classification.Results:Whereas both parameters performed similarly among glaucomatous optic neuropathy only and definite glaucoma eyes, the positive rate obtained with global RNFLT-MD was significantly greater compared with global VF-MD by 33.3% and 30.8% among ocular hypertension eyes and GVF eyes, respectively. This finding was consistent in the inferotemporal sector; however, similar positive rates were obtained for both parameters in the superotemporal sector.Conclusions:While both RNFLT and VF parameters showed comparable abilities to identify progression across the different classifications, RNFLT assessment may be better suited to monitor progression, particularly among patients with elevated intraocular pressure and those who present with only GVF defect at baseline.

Disc Hemorrhages Are Associated With the Presence and Progression of Glaucomatous Central Visual Field Defects.

In this prospective cohort study, disc hemorrhages were associated with more severe central damage on 24-2 and 10-2 visual fields (VFs), and faster progression globally on 24-2 VFs and centrally on 10-2 VFs. To study the relationship between disc hemorrhage (DH) and the presence and progression of glaucomatous central VF damage. Cross-sectional and longitudinal analyses were performed on data from the African Descent and Glaucoma Evaluation Study (ADAGES) cohort. Two masked investigators reviewed disc photographs for the presence and location of DH. 24-2 central VF damage was based on the number of test locations within the central 10 degrees of the 24-2 field pattern deviation and their mean total deviation (MTD). 10-2 central VF damage was based on pattern deviation and MTD. Main outcome measures were the association between DH and presence of central VF damage and between DH and worsening of VF. DH was detected in 21 of 335 eyes (6.2%). In the cross-sectional analysis, DH was significantly associated with more severe central damage on 24-2 [incidence rate ratio=1.47; 95% confidence interval (CI)=1.02-2.12; P=0.035] and 10-2 VFs (incidence rate ratio=1.81; 95% CI=1.26-2.60; P=0.001). In the longitudinal analysis, DH eyes progressed faster than non-DH eyes based on 24-2 global MTD rates (difference in slopes, β=-0.06; 95% CI=-0.11 to -0.01; P=0.009) and 10-2 MTD rates (β=-0.10; 95% CI=-0.14 to -0.06; P< 0.001), but not 24-2 central MTD rates (β=-0.02; 95% CI=-0.078 to 0.026; P=0.338). DH was associated with the presence and progression of central VF defects. DH identification should prompt intensive central VF monitoring and surveillance with 10-2 fields to detect progression.

The Relationship Between Intraocular Pressure and Rates of Central Versus Peripheral Visual Field Progression.

In this longitudinal prospective cohort study of open-angle glaucoma patients, intraocular pressure (IOP) parameters (mean, fluctuation, and maximum) had a similar effect on glaucomatous progression in the central and peripheral visual field (VF) regions. To study the effects of IOP on rates of glaucomatous central versus peripheral VF progression. The African Descent and Glaucoma Evaluation Study (ADAGES) is a longitudinal prospective cohort study that recruited patients from 3 centers. A sample of those with established glaucoma were included in this study. The mean peripheral sensitivity (MPS) and the mean central sensitivity (MCS) were defined based upon the average total deviation of the peripheral and central (10 degrees) points of the 24-2 VF, respectively. Progression was based upon central and peripheral change from linear mixed-effects models. The relationships between VF progression and IOP mean, maximum, and fluctuation as continuous variables were also investigated. Main outcome measures were MPS and MCS progression rates. A total of 452 eyes of 344 patients were studied. The mean number of VFs (SD) for each eye was 13.3 (6.4) over 9.1 (3.7) years. The mean baseline MD was -5.1 (3.9) dB and the mean rate of MD change was -0.26 dB/y [95% confidence interval (CI): -0.33 to -0.20, P<0.001]. Mean rates of MPS (-0.27 dB/y, 95% CI: -0.33 to -0.22, P<0.001) and MCS change (-0.26 dB/y, 95% CI: -0.31 to -0.21, P<0.001) were similar (P=0.351). Mean, fluctuation, and maximum IOP were significantly associated with MPS and MCS (all P<0.025). The effect of IOP parameters on VF progression was statistically similar between central and peripheral VF regions.

Genetic Architecture of Primary Open-Angle Glaucoma in Individuals of African Descent: The African Descent and Glaucoma Evaluation Study III

To find genetic contributions to glaucoma in African Americans. Cross-sectional, case-control study. One thousand eight hundred seventy-five primary open-angle glaucoma (POAG) patients and 1709 controls, self-identified as being of African descent (AD), from the African Descent and Glaucoma Evaluation Study (ADAGES) III and Wake Forest School of Medicine. MegaChip genotypes were imputed to Thousand Genomes data. Association of single nucleotide polymorphisms (SNPs) with POAG and advanced POAG was tested by linear mixed model correcting for relatedness and population stratification. Genetic risk scores were tested by receiver operator characteristic curves (ROC-AUCs). Primary open-angle glaucoma defined by visual field loss without other nonocular conditions (n= 1875). Advanced POAG was defined by age-based mean deviation of visual field (n= 946). Eighteen million two hundred eighty-one thousand nine hundred twenty SNPs met imputation quality of r2 > 0.7 and minor allele frequency > 0.005. Association of a novel locus, EN04, was observed for advanced POAG (rs185815146 β, 0.36; standard error, 0.065; P < 3×10-8). For POAG, an AD signal was observed at the 9p21 European descent (ED) POAG signal (rs79721419; P < 6.5×10-5) independent of the previously observed 9p21 ED signal (rs2383204; P < 2.3×10-5) by conditional analyses. An association with POAG in FNDC3B (rs111698934; P < 3.9×10-5) was observed, not in linkage disequilibrium (LD) with the previously reported ED SNP. Additional previously identified loci associated with POAG in persons of AD were: 8q22, AFAP1, and TMC01. An AUC of 0.62 was observed with an unweighted genetic risk score comprising 11 SNPs in candidate genes. Two additional risk scores were studied by using a penalized matrix decomposition with cross-validation; risk scores of 50 and 400 SNPs were identified with ROC of AUC = 0.74 and AUC = 0.94, respectively. A novel association with advanced POAG in the EN04 locus was identified putatively in persons of AD. In addition to this finding, this genome-wide association study in POAG patients of AD contributes to POAG genetics by identification of novel signals in prior loci (9p21), as well as advancing the fine mapping of regions because of shorter average LD (FNDC3B). Although not useful without confirmation and clinical trials, the use of genetic risk scores demonstrated that considerable AD-specific genetic information remains in these data.

The African Descent and Glaucoma Evaluation Study (ADAGES) III: Contribution of Genotype to Glaucoma Phenotype in African Americans: Study Design and Baseline Data

To describe the study protocol and baseline characteristics of the African Descent and Glaucoma Evaluation Study (ADAGES) III. Cross-sectional, case-control study. Three thousand two hundred sixty-six glaucoma patients and control participants without glaucoma of African or European descent were recruited from 5 study centers in different regions of the United States. Individuals of African descent (AD) and European descent (ED) with primary open-angle glaucoma (POAG) and control participants completed a detailed demographic and medical history interview. Standardized height, weight, and blood pressure measurements were obtained. Saliva and blood samples to provide serum, plasma, DNA, and RNA were collected for standardized processing. Visual fields, stereoscopic disc photographs, and details of the ophthalmic examination were obtained and transferred to the University of California, San Diego, Data Coordinating Center for standardized processing and quality review. Participant gender, age, race, body mass index, blood pressure, history of smoking and alcohol use in POAG patients and control participants were described. Ophthalmic measures included intraocular pressure, visual field mean deviation, central corneal thickness, glaucoma medication use, or past glaucoma surgery. Ocular conditions, including diabetic retinopathy, age-related macular degeneration, and past cataract surgery, were recorded. The 3266 ADAGES III study participants in this report include 2146 AD POAG patients, 695 ED POAG patients, 198 AD control participants, and 227 ED control participants. The AD POAG patients and control participants were significantly younger (both, 67.4 years) than ED POAG patients and control participants (73.4 and 70.2 years, respectively). After adjusting for age, AD POAG patients had different phenotypic characteristics compared with ED POAG patients, including higher intraocular pressure, worse visual acuity and visual field mean deviation, and thinner corneas (all P < 0.001). Family history of glaucoma did not differ between AD and ED POAG patients. With its large sample size, extensive specimen collection, and deep phenotyping of AD and ED glaucoma patients and control participants from different regions in the United States, the ADAGES IIIgenomics study will address gaps in our knowledge of the genetics of POAG in this high-risk population.

Baseline 24-2 Central Visual Field Damage Is Predictive of Global Progressive Field Loss

Central visual field (VF) damage in glaucoma patients can significantly hinder daily activities. The present study investigates whether the presence of localized baseline damage to the central 10 degrees of the VF is predictive of faster global mean deviation (MD) progression. Prospective cohort study. Eyes from the multicenter African Descent and Glaucoma Evaluation Study (ADAGES) with established glaucoma and VF loss and a minimum of 5 24-2 VFs were eligible. Baseline central 24-2 damage was defined as any of the 12 central-most points with total deviation (TD) values at P < 0.5% on 2 consecutive examinations. Progression was determined using trend-based and event-based criteria: (1) rates of MD change significantly faster than zero and (2) >-5 dB MD loss over the entire follow-up. A total of 827 eyes of 584 patients were studied. Mean rate of MD change of the entire sample was-0.15 dB/year (95% CI:-0.19 to-0.12, P<.001). Eyes with baseline central damage progressed faster than those without (difference: βcentral=-0.07 dB/year, 95% CI:-0.11 to-0.01, P= .011) and were more likely to experience MD loss greater than 5 dB (hazard ratio= 3.0 [95% CI: 2.1-4.1, P < .001]). These differences remained significant after adjusting for confounders. The presence of central VF damage at baseline is significantly associated with more rapid global progression. Detection of central VF damage aids in stratification of high-risk patients who may need intensive surveillance and aggressive treatment.

Macular Ganglion Cell Inner Plexiform Layer Thickness in Glaucomatous Eyes with Localized Retinal Nerve Fiber Layer Defects.

PurposeTo investigate macular ganglion cell–inner plexiform layer (mGCIPL) thickness in glaucomatous eyes with visible localized retinal nerve fiber layer (RNFL) defects on stereophotographs.Methods112 healthy and 149 glaucomatous eyes from the Diagnostic Innovations in Glaucoma Study (DIGS) and the African Descent and Glaucoma Evaluation Study (ADAGES) subjects had standard automated perimetry (SAP), optical coherence tomography (OCT) imaging of the macula and optic nerve head, and stereoscopic optic disc photography. Masked observers identified localized RNFL defects by grading of stereophotographs.Result47 eyes had visible localized RNFL defects on stereophotographs. Eyes with visible localized RNFL defects had significantly thinner mGCIPL thickness compared to healthy eyes (68.3 ± 11.4 μm versus 79.2 ± 6.6 μm respectively, P<0.001) and similar mGCIPL thickness to glaucomatous eyes without localized RNFL defects (68.6 ± 11.2 μm, P = 1.000). The average mGCIPL thickness in eyes with RNFL defects was 14% less than similarly aged healthy controls. For 29 eyes with a visible RNFL defect in just one hemiretina (superior or inferior) mGCIPL was thinnest in the same hemiretina in 26 eyes (90%). Eyes with inferior-temporal RNFL defects also had significantly thinner inferior-temporal mGCIPL (P<0.001) and inferior mGCIPL (P = 0.030) compared to glaucomatous eyes without a visible RNFL defect.ConclusionThe current study indicates that presence of a localized RNFL defect is likely to indicate significant macular damage, particularly in the region of the macular that topographically corresponds to the location of the RNFL defect.

African Descent and Glaucoma Evaluation Study (ADAGES): Racial Differences in Optic Disc Hemorrhage and Beta-Zone Parapapillary Atrophy

To investigate the differences in the frequency of optic disc hemorrhage (DH) and prevalence of beta-zone parapapillary atrophy (βPPA) between individuals of African descent (AD) and European descent (ED). Prospective, multicenter, observational cohort. A total of 1950 eyes of 1172 participants of the African Descent and Glaucoma Evaluation Study (ADAGES). Stereoscopic disc photographs of subjects with and without glaucomatous optic neuropathy (GON) followed during the first 13 years of the ADAGES underwent masked review searching for DH and βPPA. A total of 928 eyes (non-GON, 581; GON, 347) of 551 AD patients (non-GON, 334; GON, 217) and 1022 eyes (non-GON, 568; GON, 454) of 611 ED patients (non-GON, 334; GON, 277) were included. We compared the number of eyes with detected DH at any time during follow-up and eyes with βPPA between the AD and ED groups. The analyses were then adjusted for clinical parameters using multivariable logistic regression. Differences in frequency of DH and prevalence of βPPA. A total of 9395 stereoscopic disc photographs were reviewed. More ED eyes experience DH than AD eyes (49/1022 [4.8%] vs. 10/928 eyes [1.1%], respectively; P < 0.001), whereas βPPA had higher prevalence in AD eyes (675 eyes [72%] vs. 659 eyes [64%]; P < 0.001). In the final multivariable model, after controlling for confounders, AD eyes were less likely to have at least 1 detected DH than ED eyes (odds ratio [OR], 0.21; 95% CI, 0.10-0.45; P < 0.001) but were more likely to have βPPA than ED eyes (OR, 1.55; 95% CI, 1.12-2.14; P= 0.008). Subjects of ED are at higher risk for developing DH compared with AD subjects, whereas ADsubjects have greater prevalence of βPPA. These findings suggest that there are structural differences withinthe optic nerve complex between these groups. Further research is needed to determine whether racial differences in the frequency of DH and prevalence of βPPA affect the likelihood of glaucomatous progression.

Diagnostic Accuracy of the Spectralis and Cirrus Reference Databases in Differentiating between Healthy and Early Glaucoma Eyes

To evaluate and compare the diagnostic accuracy of global and sector analyses for detection of early visual field (VF) damage using the retinal nerve fiber layer (RNFL) reference databases of the Spectralis (Heidelberg Engineering, Heidelberg, Germany) and Cirrus (Carl Zeiss Meditec, Dublin, CA) spectral-domain optical coherence tomography (SD OCT) devices. Healthy subjects and glaucoma suspects from the Diagnostic Innovations in Glaucoma Study (DIGS) and African Descent and Glaucoma Evaluation Study (ADAGES) with at least 2 years of follow-up were included. Global and sectoral RNFL measures were classified as within normal limits, borderline (BL), and outside normal limits (ONL) on the basis of the device reference databases. The sensitivity of ONL classification was estimated in glaucoma suspect eyes that developed repeatable VF damage. A total of 353 glaucoma suspect eyes and 279 healthy eyes were included. A total of 34 (9.6%) of the glaucoma suspect eyes developed VF damage. In glaucoma suspect eyes, Spectralis and Cirrus ONL classification was present in 47 eyes (13.3%) and 24 eyes (6.8%), respectively. The sensitivity of the global RNFL ONL classification among eyes that developed VF damage was 23.5% for Cirrus and 32.4% for Spectralis. The specificity of within-normal-limits global classification in healthy eyes was 100% for Cirrus and 99.6% for Spectralis. There was moderate to substantial agreement between Cirrus and Spectralis classification as ONL. The Spectralis and Cirrus reference databases have a high specificity for identifying healthy eyes and good agreement for detection of eyes with early glaucoma damage.

Biogeographic Ancestry in the African Descent and Glaucoma Evaluation Study (ADAGES): Association With Corneal and Optic Nerve Structure

We determined if quantitative measurements of biogeographic ancestry (BGA) correlate with variations in optic disc area, corneal thickness (CCT), and retinal nerve fiber layer (RNFL) thickness. Data were obtained from 656 participants in the African Descent and Glaucoma Evaluation Study (ADAGES) cohort who consented to BGA testing. Data for CCT, optic disc area, and RNFL thickness were obtained from subjects in the ADAGES study who also had participated in the current substudy. A total of 31 ancestry informative markers (AIMs) with large allele frequencies differences between populations was used to calculate admixture proportion (implemented in STRUCTURE). Correlations with BGA adjusted for diagnosis, age, and sex for CCT and optic disc area using the whole group and RNFL thickness adjusted for age and sex for the normal study participants were determined. The mean percentage of African admixture was 79.6% in the self-described African Descent (AD) group and 3.5% in the European Descent (ED) group. Percent African ancestry was significantly correlated with CCT (ρ = -0.27, P < 0.0001) and disc area (ρ = 0.15, P < 0.0001), but only marginally associated with RNFL thickness (ρ = 0.20, P = 0.092) in adjusted models. The BGA correlates with variation in ocular features that significantly differ across racial groups and that have been associated with the development of glaucoma. While BGA can provide an objective measurement of the biologic component of self-described race for ocular research, for most nongenetic epidemiologic studies, self-described race may adequately describe the associations with these ocular characteristics. (ClinicalTrials.gov number, NCT00221923.).

The African Descent and Glaucoma Evaluation Study (ADAGES): Predictors of Visual Field Damage in Glaucoma Suspects

To evaluate racial differences in the development of visual field (VF) damage in glaucoma suspects. Prospective, observational cohort study. Six hundred thirty-six eyes from 357 glaucoma suspects with normal VF at baseline were included from the multicenter African Descent and Glaucoma Evaluation Study (ADAGES). Racial differences in the development of VF damage were examined using multivariable Cox proportional hazard models. Thirty one of 122 African-descent participants (25.4%) and 47 of 235 European-descent participants (20.0%) developed VF damage (P= .078). In multivariable analysis, worse baseline VF mean deviation, higher mean arterial pressure during follow-up, and a race ∗ mean intraocular pressure (IOP) interaction term were significantly associated with the development of VF damage, suggesting that racial differences in the risk of VF damage varied by IOP. At higher mean IOP levels, race was predictive of the development of VF damage even after adjusting for potentially confounding factors. At mean IOPs during follow-up of 22, 24, and 26mm Hg, multivariable hazard ratios (95% confidence intervals) for the development of VF damage in African-descent compared to European-descent subjects were 2.03 (1.15-3.57), 2.71 (1.39-5.29), and 3.61 (1.61-8.08), respectively. However, at lower mean IOP levels (below 22mm Hg) during follow-up, African descent was not predictive of the development of VF damage. In this cohort of glaucoma suspects with similar access to treatment, multivariate analysis revealed that at higher mean IOP during follow-up, individuals of African descent were more likely to develop VF damage than individuals of European descent.

Glaucomatous Patterns in Frequency Doubling Technology (FDT) Perimetry Data Identified by Unsupervised Machine Learning Classifiers

PurposeThe variational Bayesian independent component analysis-mixture model (VIM), an unsupervised machine-learning classifier, was used to automatically separate Matrix Frequency Doubling Technology (FDT) perimetry data into clusters of healthy and glaucomatous eyes, and to identify axes representing statistically independent patterns of defect in the glaucoma clusters.MethodsFDT measurements were obtained from 1,190 eyes with normal FDT results and 786 eyes with abnormal FDT results from the UCSD-based Diagnostic Innovations in Glaucoma Study (DIGS) and African Descent and Glaucoma Evaluation Study (ADAGES). For all eyes, VIM input was 52 threshold test points from the 24-2 test pattern, plus age.ResultsFDT mean deviation was −1.00 dB (S.D. = 2.80 dB) and −5.57 dB (S.D. = 5.09 dB) in FDT-normal eyes and FDT-abnormal eyes, respectively (p<0.001). VIM identified meaningful clusters of FDT data and positioned a set of statistically independent axes through the mean of each cluster. The optimal VIM model separated the FDT fields into 3 clusters. Cluster N contained primarily normal fields (1109/1190, specificity 93.1%) and clusters G1 and G2 combined, contained primarily abnormal fields (651/786, sensitivity 82.8%). For clusters G1 and G2 the optimal number of axes were 2 and 5, respectively. Patterns automatically generated along axes within the glaucoma clusters were similar to those known to be indicative of glaucoma. Fields located farther from the normal mean on each glaucoma axis showed increasing field defect severity.ConclusionsVIM successfully separated FDT fields from healthy and glaucoma eyes without a priori information about class membership, and identified familiar glaucomatous patterns of loss.

Predicting Progression of Glaucoma from Rates of Frequency Doubling Technology Perimetry Change

To evaluate the ability of longitudinal frequency doubling technology (FDT) to predict the development of glaucomatous visual field loss on standard automated perimetry (SAP) in glaucoma suspects. Prospective, observational cohort study. The study included 587 eyes of 367 patients with suspected glaucoma at baseline selected from the Diagnostic Innovations in Glaucoma Study (DIGS) and the African Descent and Glaucoma Evaluation Study (ADAGES). These eyes had an average of 6.7 ± 1.9 FDT tests during a mean follow-up time of 73.1 ± 28.0 months. Glaucoma suspects had intraocular pressure (IOP) >21 mmHg or an optic disc appearance suspicious of glaucoma. All patients had normal or nonrepeatable abnormal SAP at baseline. Humphrey Matrix FDT (Carl Zeiss Meditec, Inc, Dublin, CA) testing was performed within 6 months of SAP testing. The study end point was the development of 3 consecutive abnormal SAP test results. Joint longitudinal survival models were used to evaluate the ability of rates of FDT pattern standard deviation (PSD) change to predict the development of visual field loss on SAP, adjusting for confounding variables (baseline age, mean IOP, corneal thickness, and follow-up measurements of SAP PSD). The R(2) index was used to evaluate and compare the predictive abilities of the model containing longitudinal FDT PSD data with the model containing only baseline data. Sixty-three of 587 eyes (11%) developed SAP visual field loss during follow-up. The mean rate of FDT PSD change in eyes that developed SAP visual field loss was 0.07 dB/year versus 0.02 dB/year in those that did not (P < 0.001). Baseline FDT PSD and slopes of FDT PSD change were significantly predictive of progression, with hazard ratios of 1.11 per 0.1 dB higher (95% confidence interval [CI], 1.04-1.18; P = 0.002) and 4.40 per 0.1 dB/year faster (95% CI, 1.08-17.96; P = 0.04), respectively. The longitudinal model performed significantly better than the baseline model with an R(2) of 82% (95% CI, 74-89) versus 11% (95% CI, 2-24), respectively. Rates of FDT PSD change were highly predictive of the development of SAP visual field loss in glaucoma suspects. This finding suggests that longitudinal FDT evaluation may be useful for risk stratification of patients with suspected glaucoma.

The Relationship between Visual Field Index and Estimated Number of Retinal Ganglion Cells in Glaucoma

PurposeTo evaluate the relationship between visual field index (VFI) and the estimated number of retinal ganglion cells (RGCs) in glaucoma.MethodsA multicenter study of 1,245 healthy, glaucomatous and suspected glaucomatous eyes of 1,245 subjects recruited from the Diagnostic Innovations in Glaucoma Study (DIGS) and African Descent and Glaucoma Evaluation Study (ADAGES). All eyes underwent standard automated perimetry (SAP) and time-domain optical coherence tomography (TD-OCT). Estimates of RGC count and percentage of RGCs remaining, compared to age-matched healthy eyes, were calculated from TD-OCT using a previously described formula. Smoothing spline curves were fitted to examine the relationship between VFI and the percent remaining RGCs. The first derivative (i.e., slopes) of these curves was used to explore the relationship between changes in these measures.ResultsThe relationships between the VFI and both estimated RGC counts and the percent remaining RGCs were nonlinear. A unit number of VFI loss corresponded to substantially greater loss of estimated RGCs and estimated percentage of RGCs remaining in early compared to late disease.ConclusionsThe relationship between VFI and estimated RGC counts is nonlinear and the index substantially underestimates the amount of neural loss early in the disease. Disease severity should be taken into account when interpreting rates of VFI change over time.

Structure-Function Relationship in Glaucoma Using Spectral-Domain Optical Coherence Tomography

To determine the structure-function relationship in glaucoma using spectral-domain optical coherence tomography (SDOCT)-derived structural measurements and to evaluate this relationship using a linear model. In a cross-sectional study, structure-function relationships were determined for all the participants in the DIGS (Diagnostic Innovations in Glaucoma Study) and the ADAGES (African Descent and Glaucoma Evaluation Study) who had undergone standard automated perimetry (SAP) and SDOCT within 6 months of each other. Strength of relationship was reported as coefficient of determination (R(2)). The relationship was also evaluated using a previously described linear model. The results of 579 SAP and SDOCT examinations from 80 eyes of 47 control subjects, 199 eyes of 130 patients with suspected glaucoma, and 213 eyes of 146 patients with glaucoma were analyzed. The R(2) for the association between SAP total deviation and SDOCT variables ranged from 0.01 (P=.02) for the nasal rim area to 0.30 (P<.001) for inferior inner retinal thickness at the macula. The linear model fitted the data well. The strongest structure-function associations using SDOCT were found for retinal nerve fiber layer measurements at arcuate areas and inner retinal thickness at the macula measurements. The linear model is useful in studying the structure-function relationship in glaucoma.

Comparison of the Diagnostic Accuracies of the Spectralis, Cirrus, and RTVue Optical Coherence Tomography Devices in Glaucoma

To compare the diagnostic accuracies of retinal nerve fiber layer (RNFL) thickness measurements obtained with the Spectralis (Heidelberg Engineering, Dossenheim, Germany), Cirrus (Carl Zeiss Meditec, Dublin, CA), and RTVue (Optovue Inc., Fremont, CA) devices for the detection of glaucoma. Diagnostic, case-control study. A total of 233 (107 healthy, 126 glaucomatous) of 149 participants from the longitudinal Diagnostic Innovations in Glaucoma Study (DIGS) and from the African Descent and Glaucoma Evaluation Study (ADAGES). All participants underwent RNFL thickness imaging with the Spectralis, Cirrus, and RTVue devices in the same visit. Receiver operating characteristic (ROC) curves adjusted for age and race were obtained for quadrants (superior, nasal, inferior, temporal) and global RNFL thickness for all instruments. Areas under ROC (AUC) and sensitivities at fixed specificities (80% and 95%) were calculated and compared. Comparison of diagnostic accuracy using AUCs and sensitivities at fixed specificities of 80% and 95%. The RNFL thickness parameter with the largest AUCs was the superior quadrant for the Spectralis (0.88) and the global RNFL thickness for the Cirrus (0.88) and the RTVue (0.87). The pairwise comparison among the ROC curves showed no statistical difference for all parameters except for the nasal quadrant, which had significantly larger AUC in the Spectralis and RTVue compared with the Cirrus (P<0.03 for both comparisons). There were no significant differences in sensitivities among the best parameters from each instrument (P>0.05). The superior quadrant thickness measured with the Spectralis had sensitivity of 81.9% at a fixed specificity of 80% and 70% at a fixed specificity of 95%. The global thickness measured by the Cirrus had a sensitivity of 80.3% at a fixed specificity of 80% and 65.6% at a fixed specificity of 95%. For the RTVue, the global thickness had a sensitivity of 77.9% at a fixed specificity of 80% and 62.1% at a fixed specificity of 95%. Although the spectral-domain optic coherence tomography (SD-OCT) instruments have different resolution and acquisition rates, their ability to detect glaucoma was similar.

Comparison of Corneal Biomechanical Properties Between Healthy Blacks and Whites Using the Ocular Response Analyzer

To analyze and compare corneal biomechanical properties in healthy black and white subjects using the Ocular Response Analyzer (ORA) and to evaluate their relationship with other ocular parameters. Observational cross-sectional study. One hundred eighty one eyes (46 in blacks, 135 in whites) of 119 patients (37 blacks, 82 whites) were recruited from the longitudinal Diagnostic Innovations in Glaucoma Study (DIGS) and from the African Descent and Glaucoma Evaluation Study (ADAGES) at the University of California, San Diego. Corneal curvature, axial length, central corneal thickness (CCT), corneal hysteresis (CH), and corneal resistance factor (CRF) were obtained from all participants. Univariable and multivariable regression analyses were used to evaluate the associations between ORA measurements and age, CCT, axial length, corneal curvature, and race. Black subjects had significantly lower values of CH (9.7 mm Hg vs 10.4 mm Hg; P = .033), CRF (9.84 mm Hg vs 10.70 mm Hg; P = .028), and CCT (534 mum vs 562 mum; P = .001) compared to white subjects. A significant relationship was found between CH and CCT (R(2) = 0.25; P < .001) and between CRF and CCT (R(2) = 0.42; P < .001). After adjusting for CCT, age, axial length, and corneal curvature, the difference between blacks and whites in CH (P = .077) and CRF (P = .621) measurements lost statistical significance. Black subjects tended to have lower measurements of corneal hysteresis compared to white subjects; however, this was largely explained by differences in corneal thickness. Therefore, it is unlikely that CH would have an independent effect in explaining differences in susceptibility of disease between these 2 racial groups.

African Descent and Glaucoma Evaluation Study (ADAGES)

To define differences in optic disc, retinal nerve fiber layer, and macular structure between healthy participants of African (AD) and European descent (ED) using quantitative imaging techniques in the African Descent and Glaucoma Evaluation Study (ADAGES). Reliable images were obtained using stereoscopic photography, confocal scanning laser ophthalmoscopy (Heidelberg retina tomography [HRT]), and optical coherence tomography (OCT) for 648 healthy subjects in ADAGES. Findings were compared and adjusted for age, optic disc area, and reference plane height where appropriate. The AD participants had significantly greater optic disc area on HRT (2.06 mm(2); P < .001) and OCT (2.47 mm(2); P < .001) and a deeper HRT cup depth than the ED group (P < .001). Retinal nerve fiber layer thickness was greater in the AD group except within the temporal region, where it was significantly thinner. Central macular thickness and volume were less in the AD group. Most of the variations in optic nerve morphologic characteristics between the AD and ED groups are due to differences in disc area. However, differences remain in HRT cup depth, OCT macular thickness and volume, and OCT retinal nerve fiber layer thickness independent of these variables. These differences should be considered in the determination of disease status.