Standard Automated Perimetry Sensitivity Research Articles

Comparison of the Structure-Function Relationship in Glaucoma Using Optical Microangiography in the Peripapillary Retinal Nerve Fiber Layer.

Optical microangiography measurements correlated with functional parameters in glaucoma patients. Optical coherence tomography angiography-derived vessel perfusion density (VPD) better reflected the structure-function relationship than flux index (FI) and retinal nerve fiber layer thickness. The purpose of this study was to compare the structure-function relationship between peripapillary optical microangiography (OMAG) measurements and standard automated perimetry (SAP) loss by comparison with peripapillary retinal nerve fiber layer (pRNFL) thickness in primary open-angle glaucoma. One eye from each of 128 patients with early-to-severe glaucoma (including preperimetric glaucoma) and 23 normal participants underwent optic nerve head scanning of the radial peripapillary capillaries and pRNFL scans with OMAG centered on the optic disc and SAP (mean age: 67.8±12.0 y; SAP mean deviation: -5.84±6.6 dB). Regional relationships between VPD, FI, pRNFL thickness, and corresponding SAP sensitivity were compared using linear and fractional polynomial (FP) models. Structure was significantly related to function for all but the nasal pRNFL thickness region. For VPD, the coefficient of determination (R2) using the FP model was significantly stronger than that of the linear model (FP: 0.25 to 0.67, linear: 0.19 to 0.61), while no difference was found for FI in any region (FP: 0.19 to 0.44, linear: 0.15 to 0.42). R2 for VPD was stronger than FI and pRNFL (FP: 0.11 to 0.52, linear: 0.01 to 0.44) in inferior and superior regions, while VPD and FI were not different in temporal and nasal regions. VPD showed a stronger association with visual field loss than FI or retinal nerve fiber layer thickness except in the temporal region. The FI relationship was weak but more linear around the peripapillary region. The strength of the structure-function relationship may differ depending on the region of OMAG measurements.

Slowed Saccadic Reaction Times in Seemingly Normal Parts of Glaucomatous Visual Fields.

Purpose: In eye movement perimetry, peripheral stimuli are confirmed by goal-directed eye movements toward the stimulus. The saccadic reaction time (SRT) is regarded as an index of visual field responsiveness, whereas in standard automated perimetry (SAP), the visual field sensitivity is tested. We investigated the relation between visual field sensitivity and responsiveness in corresponding locations of the visual field in healthy controls and in patients with mild, moderate and advanced glaucoma.Materials and Methods: Thirty-four healthy control subjects and 42 glaucoma patients underwent a 54-point protocol in eye movement perimetry (EMP) and a 24-2 SITA standard protocol in a Humphrey Field Analyzer. The visual field points were stratified by total deviation sensitivity loss in SAP into 6 strata. A generalized linear mixed model was applied to determine the influence of the various factors.Results: The generalized linear mixed model showed that the mean SRT increased with increasing glaucoma severity, from 479 ms in the control eyes to 678 ms in the eyes of patients with advanced glaucoma (p < 0.001). Mean SRTs significantly increased with increasing SAP sensitivity loss. Even at the locations where no sensitivity loss was detected by SAP (total deviation values greater or equal than 0 dB), we found lengthened SRTs in mild, moderate and advanced glaucoma compared to healthy controls (p < 0.05) and in moderate and advanced glaucoma compared to mild glaucoma (p < 0.05). At locations with total deviation values between 0 and −3 dB, −3 and −6 dB and −6 and −12 dB, we found similar differences.Conclusions: The lengthened SRT in areas with normal retinal sensitivities in glaucomatous eyes, i.e., planning and execution of saccades to specific locations, precede altered sensory perception as assessed with SAP. Better understanding of altered sensory processing in glaucoma might allow earlier diagnosis of emerging glaucoma.

A case control study examining the feasibility of using eye tracking perimetry to differentiate patients with glaucoma from healthy controls

To explore the feasibility of using Saccadic Vector Optokinetic Perimetry (SVOP) to differentiate glaucomatous and healthy eyes. A prospective case–control study was performed using a convenience sample recruited from a single university glaucoma clinic and a group of healthy controls. SVOP and standard automated perimetry (SAP) was performed with testing order randomised. The reference standard was a diagnosis of glaucoma based a comprehensive ophthalmic examination and abnormality on standard automated perimetry (SAP). The index test was SVOP. 31 patients with glaucoma and 24 healthy subjects were included. Mean SAP mean deviation (MD) in those with glaucoma was − 8.7 ± 7.4 dB, with mean SAP and SVOP sensitivities of 23.3 ± 0.9 dB and 22.1 ± 4.3 dB respectively. Participants with glaucoma were significantly older. On average, SAP sensitivity was 1.2 ± 1.4 dB higher than SVOP (95% limits of agreement = − 1.6 to 4.0 dB). SVOP sensitivity had good ability to differentiate healthy and glaucomatous eyes with a 95% CI for area under the curve (AUC) of 0.84 to 0.96, similar to the performance of SAP sensitivity (95% CI 0.86 to 0.97, P = 0.60). For 80% specificity, SVOP had a 95% CI sensitivity of 75.7% to 94.8% compared to 77.8% to 96.0% for SAP. SVOP took considerably longer to perform (514 ± 54 s compared to 267 ± 76 s for SAP). Eye tracking perimetry may be useful for detection of glaucoma but further studies are needed to evaluate SVOP within its intended sphere of use, using an appropriate design and independent reference standard.

Speed and accuracy of saccades in patients with glaucoma evaluated using an eye tracking perimeter

BackgroundTo examine the speed and accuracy of saccadic eye movements during a novel eye tracking threshold visual field assessment and determine whether eye movement parameters may improve ability to detect glaucoma.MethodsA prospective study including both eyes of 31 patients with glaucoma and 23 controls. Standard automated perimetry (SAP) and eye tracking perimetry (saccadic vector optokinetic perimetry, SVOP) was performed. SVOP provided data on threshold sensitivity, saccade latency, and two measures of accuracy of saccades (direction bias and amplitude bias). The relationship between eye movement parameters and severity of glaucoma was examined and Receiver Operating Characteristic curves were used to assess ability to detect glaucoma.ResultsPatients with glaucoma had significantly slower saccades (602.9 ± 50.0 ms versus 578.3 ± 44.6 ms for controls, P = 0.009) and reduced saccade accuracy (direction bias = 7.4 ± 1.8 versus 6.5 ± 1.5 degrees, P = 0.006). There was a significant slowing of saccades and saccades became less accurate with worsening SAP sensitivity. Slower saccades were associated with increased odds of glaucoma; however, the AUC for saccade latency was only 0.635 compared to 0.914 for SVOP sensitivity.ConclusionPatients with glaucoma had significant differences in eye movements compared to healthy subjects, with a relationship between slower and less accurate eye movements and worse glaucoma severity. However, in a multivariable model, eye movement parameters were not of additional benefit in differentiating eyes with glaucoma from healthy controls.

Artificial Intelligence Mapping of Structure to Function in Glaucoma.

PurposeTo develop an artificial intelligence (AI)–based structure-function (SF) map relating retinal nerve fiber layer (RNFL) damage on spectral domain optical coherence tomography (SDOCT) to functional loss on standard automated perimetry (SAP).MethodsThe study included 26,499 pairs of SAP and SDOCT from 15,173 eyes of 8878 patients with glaucoma or suspected of having the disease extracted from the Duke Glaucoma Registry. The data set was randomly divided at the patient level in training and test sets. A convolutional neural network (CNN) was initially trained and validated to predict the 52 sensitivity threshold points of the 24-2 SAP from the 768 RNFL thickness points of the SDOCT peripapillary scan. Simulated localized RNFL defects of varied locations and depths were created by modifying the normal average peripapillary RNFL profile. The simulated profiles were then fed to the previously trained CNN, and the topographic SF relationships between structural defects and SAP functional losses were investigated.ResultsThe CNN predictions had an average correlation coefficient of 0.60 (P < 0.001) with the measured values from SAP and a mean absolute error of 4.25 dB. Simulated RNFL defects led to well-defined arcuate or paracentral visual field losses in the opposite hemifield, which varied according to the location and depth of the simulations.ConclusionsA CNN was capable of predicting SAP sensitivity thresholds from SDOCT RNFL thickness measurements and generate an SF map from simulated defects.Translational RelevanceAI-based SF map improves the understanding of how SDOCT losses translate into detectable SAP damage.

The ability of eye tracking perimetry to detect glaucoma

AbstractPurposeTo examine the diagnostic ability of saccadic vector optokinetic perimetry (SVOP), a new eye tracking perimeter, by assessing its capacity to differentiate healthy and glaucomatous participants, and to compare performance to standard automated perimetry (SAP).MethodsA prospective case‐control study including patients with glaucoma and healthy volunteers recruited from the glaucoma clinic at a university hospital and from the Scottish Health Research Register (SHARE). Participants underwent a comprehensive ophthalmic examination and performed SAP and SVOP in both eyes with the order of testing randomised.Results61 eyes of 31 participants with glaucoma and 47 eyes of 24 healthy participants were included in the study. Average SAP mean deviation (MD) in glaucomatous eyes was ‐8.72 ± 7.37 dB, with average SAP and SVOP sensitivities of 23.28 ± 0.89 dB and 22.1 ± 4.25 dB respectively. There was strong correlation between average SAP and SVOP sensitivities (r = 0.951 , P&lt;0.001). On average, SAP sensitivity was 1.16 ± 1.43 dB higher than SVOP sensitivity, with 95% limits of agreement of ‐1.64 to 3.96 dB. SVOP average sensitivity had excellent ability to differentiate healthy and glaucomatous eyes with an AUC of 0.90 (95% CI 0.84 to 0.96), which was not significantly different to the performance of SAP average sensitivity (AUC = 0.92, 95% CI .0.86 to 0.97, P = 0.60) (Figure 6). SVOP had 85.2% sensitivity for 80% specificity, compared to 86.9% sensitivity for 80% specificity for SAP.ConclusionsThe results of this study suggest that eye tracking perimetry using SVOP could offer a feasible alternative to SAP for detection of glaucoma. Overall, there was good agreement between differential light sensitivity values measured using SVOP and those measured using SAP, and average SVOP and SAP sensitivities had similarly good ability to differentiate glaucomatous and healthy eyes.

Ganglion cell layer segmentation and the two-flash multifocal electroretinogram improve structure function analysis in early glaucoma

PurposeTo improve structure-function analysis in primary open-angle glaucoma (POAG) by including the two-global flash multifocal electroretinogram (2F–mfERG) and macular ganglion cell layer segmentation.MethodsTwenty-five glaucoma patients (six pre-perimetric (PPG), 19 POAG) and 16 controls underwent 2F–mfERG, optical coherence tomography (OCT), and standard automated perimetry (SAP). For 2F–mfERG, the root mean square was calculated for the focal flash response at 15–45 ms (DC) and the global flash responses at 45–75 ms (IC1) and 75–105 ms (IC2). For OCT, macular total thickness (mT) and ganglion cell-inner plexiform layer (GCIPL) thickness were analysed. Values from the central 10° and 15° of 2F-mfERG were compared to the corresponding areas from OCT and visual field.ResultsBoth PPG and POAG had significantly lower mfERG responses in the central 10° and 15° than the control group. Of the glaucoma patients, 30.7% (three PPG, five POAG) showed central mfERG and GCIPL reduction without a SAP defect in the central 15 degrees. Four patients had a central SAP defect associated with a reduced GCIPL without any detectable dysfunction on mfERG. MfERG DC and IC2 were larger with increased mT (p ≤ 0.02), but GCIPL only related positively to IC2 (p = 0.027). SAP sensitivity also increased with thicker mT but not with GCIPL (p < 0.03 and p = 0.35). DC, IC2, and GCIPL could best differentiate glaucoma from control (AUC values: 0.897, 0.903, and 0.905).ConclusionsStructure function analysis in glaucoma can be improved when the GCIPL thickness as well as the 2F–mfERG is included as these measures complement information obtained by SAP.

The Estimates of Retinal Ganglion Cell Counts Performed Better than Isolated Structure and Functional Tests for Glaucoma Diagnosis.

Purpose To evaluate the diagnostic accuracy of retinal ganglion cell (RGC) counts as estimated by combining data from standard automated perimetry (SAP) and spectral domain optical coherence tomography (SD-OCT). Methods Healthy individuals and glaucoma patients were included in this cross-sectional study. All eyes underwent 24-2 SITA SAP and structural imaging tests. RGC count estimates were obtained using a previously described algorithm, which combines estimates of RGC numbers from SAP sensitivity thresholds and SD-OCT retinal nerve fiber layer (RNFL) average thickness. Results A total of 119 eyes were evaluated, including 75 eyes of 48 healthy individuals and 44 eyes of 29 glaucoma patients. RGC count estimates performed better than data derived from SD-OCT RNFL average thickness or SAP mean deviation alone (area under ROC curves: 0.98, 0.92, and 0.79; P < 0.001) for discriminating healthy from glaucomatous eyes, even in a subgroup of eyes with mild disease (0.97, 0.88, and 0.75; P < 0.001). There was a strong and significant correlation between estimates of RGC numbers derived from SAP and SD-OCT (R2 = 0.74; P < 0.001). Conclusion RGC count estimates obtained by combined structural and functional data showed excellent diagnostic accuracy for discriminating the healthy from the glaucomatous eyes and performed better than isolated structural and functional parameters.

Correlation of Macular Ganglion Cell Complex Thickness With Frequency-doubling Technology Perimetry in Open-angle Glaucoma With Hemifield Defects.

To understand better the relationship between the macular ganglion cell complex (mGCC) thickness and visual field sensitivity assessed by frequency-doubling technology (FDT) perimetry in the standard automated perimetry (SAP) normal hemifields of glaucomatous eyes, a model of preperimetric stage of glaucoma. Thirty-four eyes of 34 patients with glaucomatous visual field defects restricted to the superior or inferior hemifield were included. Patients underwent the mGCC and circumpapillary retinal nerve fiber layer (cpRNFL) thickness measurements using spectral domain optical coherence tomography and the FDT testing with N-30 full-threshold protocol. SAP and FDT sensitivity values were averaged in the area corresponding to thickness measurements and the thickness sensitivity relationships were assessed in the SAP normal and SAP abnormal halves (Spearman's rank correlation coefficient). FDT sensitivity was significantly correlated with both the cpRNFL and mGCC thicknesses either in the SAP normal (ρ=0.384 and 0.462, respectively) or in the SAP abnormal (ρ=0.402 and 0.717, respectively) halves. Correlation between the FDT sensitivity and the mGCC thickness was significantly (P=0.016) stronger than that with the cpRNFL thickness in the SAP abnormal half. SAP sensitivity was correlated significantly (ρ=0.570) only with the mGCC thickness in the SAP abnormal half. Similarly strong correlations of the mGCC thickness with the FDT sensitivity in the SAP normal and SAP abnormal halves, but not with the SAP sensitivity, indicates that the mGCC thickness and the FDT sensitivity may be more optimal structure-function indicator in preperimetric stage of glaucoma.

Fast Visual Field Progression Is Associated with Depressive Symptoms in Patients with Glaucoma

To evaluate the association between the rates of progressive visual field loss and the occurrence of depressive symptoms in patients with glaucoma followed over time. Prospective observational cohort study. The study included 204 eyes of 102 patients with glaucomatous visual field defects on standard automated perimetry (SAP). All patients had Geriatric Depression Scale (GDS) questionnaires and visual field tests obtained over a mean follow-up time of 2.2±0.6 years. Change in depressive symptoms was assessed by calculating the difference between GDS scores at the last follow-up visit from those at baseline. Rates of visual field loss were assessed by SAP. An integrated binocular visual field was estimated from the monocular SAP tests, and rates of change in mean sensitivity (MS) over time were obtained from linear mixed models. Regression models were used to investigate the association between progressive visual field loss and changes in depressive symptoms, adjusting for potentially confounding clinical and socioeconomic variables. The association between rates of change in binocular SAP MS and change in GDS questionnaire scores. There was a significant correlation between change in the GDS scores during follow-up and change in binocular SAP sensitivity. Each 1 decibel (dB)/year change in binocular SAP MS was associated with a change of 2.0 units in the GDS scores during the follow-up period (P = 0.025). In a multivariable model adjusting for baseline disease severity, change in visual acuity, age, gender, race, Montreal Cognitive Assessment score, education, income, and comorbidity index, each 1 dB/year change in binocular SAP MS was associated with a change of 3.0 units in the GDS score (P = 0.019). Faster visual field progression was associated with the occurrence of depressive symptoms in patients with glaucoma.

Relationship Between Motor Vehicle Collisions and Results of Perimetry, Useful Field of View, and Driving Simulation in Drivers With Glaucoma.

To examine the relationship between Motor Vehicle Collisions (MVCs) in drivers with glaucoma and standard automated perimetry (SAP), Useful Field of View (UFOV), and driving simulator assessment of divided attention. A cross-sectional study of 153 drivers from the Diagnostic Innovations in Glaucoma Study. All subjects had SAP and divided attention was assessed using UFOV and driving simulation using low-, medium-, and high-contrast peripheral stimuli presented during curve negotiation and car following tasks. Self-reported history of MVCs and average mileage driven were recorded. Eighteen of 153 subjects (11.8%) reported a MVC. There was no difference in visual acuity but the MVC group was older, drove fewer miles, and had worse binocular SAP sensitivity, contrast sensitivity, and ability to divide attention (UFOV and driving simulation). Low contrast driving simulator tasks were the best discriminators of MVC (AUC 0.80 for curve negotiation versus 0.69 for binocular SAP and 0.59 for UFOV). Adjusting for confounding factors, longer reaction times to driving simulator divided attention tasks provided additional value compared with SAP and UFOV, with a 1 standard deviation (SD) increase in reaction time (approximately 0.75 s) associated with almost two-fold increased odds of MVC. Reaction times to low contrast divided attention tasks during driving simulation were significantly associated with history of MVC, performing better than conventional perimetric tests and UFOV. The association between conventional tests of visual function and MVCs in drivers with glaucoma is weak, however, tests of divided attention, particularly using driving simulation, may improve risk assessment.

Association between progressive retinal nerve fiber layer loss and longitudinal change in quality of life in glaucoma.

Evaluation of structural optic nerve damage is a fundamental part of diagnosis and management of glaucoma. However, the relationship between structural measurements and disability associated with the disease is not well characterized. Quantification of this relationship may help validate structural measurements as markers directly relevant to quality of life. To evaluate the relationship between rates of retinal nerve fiber layer (RNFL) loss and longitudinal changes in quality of life in glaucoma. Observational cohort study including 260 eyes of 130 patients with glaucoma followed up for a mean (SD) of 3.5 (0.7) years. All patients had repeatable visual field defects on standard automated perimetry (SAP) at baseline. The 25-item National Eye Institute Visual Function Questionnaire (NEI VFQ-25) was performed annually, and spectral-domain optical coherence tomography and SAP were performed at 6-month intervals. A joint model was used to investigate the association between change in NEI VFQ-25 Rasch-calibrated scores and change in RNFL thickness, adjusting for confounding socioeconomic and clinical variables. Association between change in binocular RNFL thickness (RNFL thickness in the better eye at each point) and change in NEI VFQ-25 scores. Progressive binocular RNFL thickness loss was associated with worsening of NEI VFQ-25 scores over time. In a multivariable model adjusting for baseline disease severity and the rate of change in binocular SAP sensitivity, each 1-μm-per-year loss of RNFL thickness was associated with a decrease of 1.3 units (95% CI, 1.02-1.56) per year in NEI VFQ-25 scores (P < .001). After adjusting for the contribution from SAP, 26% (95% CI, 12%-39%) of the variability of change in NEI VFQ-25 scores was associated uniquely with change in binocular RNFL thickness. The P value remained less than .001 after adjusting for potential confounding factors. Progressive binocular RNFL thickness loss was associated with longitudinal loss in quality of life, even after adjustment for progressive visual field loss. These findings suggest that rates of binocular RNFL change are valid markers for the degree of neural loss in glaucoma with significant relationship to glaucoma-associated disability.

Longitudinal Changes in Quality of Life and Rates of Progressive Visual Field Loss in Glaucoma Patients

To evaluate the association between longitudinal changes in quality of life (QoL) and rates of progressive visual field loss in glaucoma. Prospective observational cohort study. We recruited 322 eyes of 161 patients with glaucomatous visual field loss from the Diagnostic Innovations Glaucoma Study followed for an average of 3.5±0.7 years. All subjects had National Eye Institute Visual Function Questionnaire (NEI VFQ)-25 performed annually and standard automated perimetry (SAP) at 6-month intervals. Subjects were included if they had a minimum of 2 NEI VFQ-25 and ≥5 SAP during follow-up. Evaluation of rates of visual field change was performed using the mean sensitivity (MS) of the integrated binocular visual field (BVF). Rasch analysis was performed to obtain final scores of disability as measured by the NEI VFQ-25. A joint longitudinal multivariate mixed model was used to investigate the association between change in NEI VFQ-25 Rasch-calibrated scores and change in BVF sensitivity. Potentially confounding socioeconomic and clinical variables also were analyzed. The relationship between change in NEI VFQ-25 Rasch-calibrated scores and change in binocular SAP MS. There was a significant correlation between change in the NEI VFQ-25 Rasch scores during follow-up and change in binocular SAP sensitivity. Each 1-dB change in binocular SAP MS per year was associated with a change of 2.9 units per year in the NEI VFQ-25 Rasch scores during the follow-up period (R(2)= 26%; P<0.001). Eyes with more severe disease at baseline were also more likely to have a decrease in NEI VFQ-25 scores during follow-up (P<0.001). For subjects with the same amount of change in SAP sensitivity, those with shorter follow-up times had larger changes in NEI VFQ-25 scores (P= 0.005). A multivariable model containing baseline and rate of change in binocular MS had an adjusted R(2) of 50% in predicting change in NEI VFQ-25 scores. Baseline severity, magnitude, and rates of change in BVF sensitivity were associated with longitudinal changes in QoL of glaucoma patients. Assessment of longitudinal visual field changes may help to identify patients at greater risk for developing disability from the disease.

Relationship between macular inner retinal layer thickness and corresponding retinal sensitivity in normal eyes.

The correlation between standard automated perimetry (SAP) sensitivity and macular inner retinal layer thickness in eyes with glaucoma is well known. We examined whether the corresponding correlation is also significant in normal eyes. One eye of each of 195 normal subjects was included. The average thickness of the macular ganglion cell-inner plexiform layers (GCIPL) and the macular retinal nerve fiber layer/GCIPL (ganglion cell complex, GCC) in four regions with 0.6-mm-diameter circular area corresponding to the four central test points of the Humphrey Field Analyzer 24-2 test program, adjusted for ganglion cell displacement, were measured using spectral-domain optical coherence tomography (SD-OCT) and correlated to the mean SAP sensitivity (in 1/Lambert scale) at the corresponding test points with a multiple regression analysis using age, refraction, disc size, sex, and laterality of the eye as other explanatory variables. In normal eyes, GCIPL and GCC thickness (in micrometers) showed significant correlation to SAP sensitivity in corresponding areas, with partial regression coefficients of 0.0016 (P = 0.036) and 0.0022 (P = 0.023), respectively. Other significantly correlated factors were age and GCIPL (-0.18, P = 0.000), age and GCC (-0.20, P = 0.000), and refraction and GCIPL (0.92, P = 0.012). Similar analyses at each of the four test points yielded essentially the same results, although partial correlation coefficients were not always significant. A thicker macular GCIPL or GCC was weakly but significantly associated with higher SAP sensitivity in the corresponding macular region in normal eyes.

Relationship between Ganglion Cell Layer Thickness and Estimated Retinal Ganglion Cell Counts in the Glaucomatous Macula

To investigate the relationship between macular ganglion cell-inner plexiform layer (mGCIPL) thickness and estimated macular retinal ganglion cell (RGC) counts in glaucoma. Observational cohort study. Cross-sectional study of 77 healthy, 154 glaucoma suspect, and 159 glaucomatous eyes from the Diagnostic Innovations in Glaucoma Study. All eyes underwent 24-2 standard automated perimetry (SAP) and optic nerve and macular imaging using high-definition optical coherence tomography (OCT). The total number of RGCs was estimated using a previously described model that uses SAP and OCT circumpapillary retinal nerve fiber layer (cpRNFL) measurements. The number of macular RGCs was estimated from the temporal cpRNFL and SAP test points within the central 10°. The correlation between mGCIPL thickness and estimates of macular RGC counts. The average estimated macular RGC count in glaucomatous eyes was 306 010 ± 109 449 cells, which was significantly lower than the estimate of 520 678 ± 106 843 cells in healthy eyes (P < 0.001). Glaucomatous eyes had 41% fewer estimated macular RGCs than healthy eyes and suspects had 21% fewer estimated macular RGCs. There was strong correlation between estimated macular RGC counts and mGCIPL thickness (R(2) = 0.67; P < 0.001). Macular RGC counts performed better than average mGCIPL thickness in discriminating healthy and glaucomatous eyes with receiver operating characteristic curve areas of 0.873 and 0.775, respectively (P = 0.015). The strong association between estimated macular RGC counts and mGCIPL thickness and the better diagnostic performance of the macular RGC counts compared with mGCIPL thickness provides further evidence that estimates of RGC number from cpRNFL thickness and SAP sensitivity can be used to assess neural losses in glaucoma.

Glaucomatous Retinal Nerve Fiber Layer Thickness Loss Is Associated With Slower Reaction Times Under a Divided Attention Task

To examine the relationship between glaucomatous structural damage and ability to divide attention during simulated driving. Cross-sectional observational study. Hamilton Glaucoma Center, University of California San Diego. Total of 158 subjects from the Diagnostic Innovations in Glaucoma Study, including 82 with glaucoma and 76 similarly aged controls. Ability to divide attention was investigated by measuring reaction times to peripheral stimuli (at low, medium, or high contrast) while concomitantly performing a central driving task (car following or curve negotiation). All subjects had standard automated perimetry (SAP) and optical coherence tomography was used to measure retinal nerve fiber layer (RNFL) thickness. Cognitive ability was assessed using the Montreal Cognitive Assessment and subjects completed a driving history questionnaire. Reaction times to the driving simulator divided attention task. The mean reaction times to the low-contrast stimulus were 1.05 s and 0.64 s in glaucoma and controls, respectively, during curve negotiation (P < .001), and 1.19 s and 0.77 s (P = .025), respectively, during car following. There was a nonlinear relationship between reaction times and RNFL thickness in the better eye. RNFL thickness remained significantly associated with reaction times even after adjusting for age, SAP mean deviation in the better eye, cognitive ability, and central driving task performance. Although worse SAP sensitivity was associated with worse ability to divide attention, RNFL thickness measurements provided additional information. Information from structural tests may improve our ability to determine which patients are likely to have problems performing daily activities, such as driving.

The Relationship Between Cup-to-Disc Ratio and Estimated Number of Retinal Ganglion Cells

To investigate the relationship between cup-to-disc ratio (CDR) and estimates of retinal ganglion cell (RGC) number. This cross-sectional study included 156 healthy eyes, 53 glaucoma suspects, and 127 eyes with glaucoma. All eyes had standard automated perimetry (SAP), Cirrus SD-OCT, and stereoscopic optic disc photography within 6 months. CDR was determined from stereoscopic photographs by two or more masked graders. The number of RGCs in each eye was estimated using a published model that combines estimates of RGC number from SAP sensitivity thresholds and SD-OCT retinal nerve fiber layer measurements. The mean estimated RGC count was 1,063,809 in healthy eyes; 828,522 in eyes with suspected glaucoma; and 774,200 in early, 468,568 in moderate, and 218,471 in advanced glaucoma. Healthy eyes had a mean vertical CDR of 0.45 ± 0.15 vs. 0.80 ± 0.16 in glaucomatous eyes. There was good correlation between stereophotographic vertical CDR and SD-OCT vertical CDR (R(2) = 0.825; P < 0.001). The relationship between estimated RGCs and vertical CDR was best represented using a third degree polynomial regression model, including age and optic disc area, which accounted for 83.3% of the variation in estimated RGC counts. The nonlinear relationship between RGC estimates and CDRs indicated that eyes with a large CDR would require loss of large RGC numbers for a small increase in CDR. The relationship between estimated RGC counts and CDR suggests that assessment of change in CDR is an insensitive method for evaluation of progressive neural losses in glaucoma. Even relatively small changes in CDR may be associated with large losses of RGCs, especially in eyes with large CDRs. (ClinicalTrials.gov numbers, NCT00221923, NCT00221897.).

Retinal Ganglion Cell Count Estimates Associated with Early Development of Visual Field Defects in Glaucoma

To estimate retinal ganglion cell (RGC) losses associated with the earliest development of visual field defects in glaucoma. Observational cohort study. The study group included 53 eyes of 53 patients with suspected glaucoma who were followed as part of the Diagnostic Innovations in Glaucoma (DIGS) study. These eyes had normal standard automated perimetry (SAP) visual fields at baseline and developed repeatable (3 consecutive) abnormal test results during a median follow-up of 6.7 years. An age-matched control group of 124 eyes of 124 healthy subjects recruited from the general population was included. Estimates of RGC counts were obtained using a previously published model that combines estimates of RGC numbers from SAP sensitivity thresholds and retinal nerve fiber layer (RNFL) thickness measurements with spectral domain optical coherence tomography (SD-OCT). For eyes converting to glaucoma, estimates of RGC counts were obtained at the time (within ± 3 months) of the first abnormal visual field, representing the time of earliest detection of visual field losses. Estimates of RGC counts in eyes converting to glaucoma versus healthy eyes. The average RGC count estimate in the eyes with early visual field defects was 652057 ± 115829 cells, which was significantly lower than the average of 910 584 ± 142 412 cells found in healthy eyes (P < 0.001). Compared with the average number of RGCs in the healthy group, glaucomatous eyes had an average RGC loss of 28.4%, ranging from 6% to 57%, at the time of the earliest visual field defect on SAP. Retinal ganglion cell counts performed significantly better than the SD-OCT average RNFL thickness parameter in discriminating glaucomatous from healthy eyes with receiver operating characteristic curve areas of 0.95 ± 0.02 versus 0.88 ± 0.03, respectively (P = 0.001). Glaucomatous eyes with the earliest detectable visual field loss on automated perimetry may already show substantial loss of RGCs. Empirical estimates of RGC counts combining structural and functional tests agreed closely with previous histologic reports on the number of RGCs associated with early visual fields defects on SAP.

Correlation Between Retinal Nerve Fiber Layer Thickness and Visual Field Sensitivity: Diffuse Atrophy Imaging Study

To identify the correlation between retinal nerve fiber layer (RNFL) thickness and visual field sensitivity in healthy eyes with preperimetric and perimetric glaucoma and to estimate the functional RNFL loss in eyes with pre-perimetric glaucoma. One hundred and two eyes with glaucoma and diffuse RNFL atrophy and 102 healthy eyes were enrolled. The correlation between optical coherence tomography (OCT)-measured RNFL thickness of the superior (clock-hour segments 10, 11, 12, 1, 2, and 3) and inferior (clock-hour segments 5, 6, 7, and 8) area and the average total deviations of the inferior and superior hemifields in standard automated perimetry (SAP) were evaluated using the simple linear model, respectively. The OCT-measured RNFL thickness was assumed to comprise functional and residual thicknesses; the residual thickness was calculated from the simple linear model and the eyes with severe diffuse RNFL atrophy. Functional RNFL thickness was compared between groups. Twenty-seven eyes had preperimetric and 75 eyes had perimetric glaucoma. The coefficient of determination (R(2)) of the simple linear model was 0.71 to 0.77 for the correlation between RNFL thickness and total deviation of SAP. The estimated residual thickness was 50.4 to 56.5 μm. On comparison with normal eyes, eyes with preperimetric glaucoma were estimated to have 37% to 41% functional RNFL loss. The correlation between RNFL thickness and SAP sensitivity was well explained by the simple linear model. Approximately 40% loss of the functional RNFL was found in preperimetric glaucoma.

Evaluation of baseline structural factors for predicting glaucomatous visual-field progression using optical coherence tomography, scanning laser polarimetry and confocal scanning laser ophthalmoscopy

The objective of this study is to assess whether baseline optic nerve head (ONH) topography and retinal nerve fiber layer thickness (RNFLT) are predictive of glaucomatous visual-field progression in glaucoma suspect (GS) and glaucomatous eyes, and to calculate the level of risk associated with each of these parameters. Participants with ≥28 months of follow-up were recruited from the longitudinal Advanced Imaging for Glaucoma Study. All eyes underwent standard automated perimetry (SAP), confocal scanning laser ophthalmoscopy (CSLO), time-domain optical coherence tomography (TDOCT), and scanning laser polarimetry using enhanced corneal compensation (SLPECC) every 6 months. Visual-field progression was assessed using pointwise linear-regression analysis of SAP sensitivity values (progressor) and defined as significant sensitivity loss of >1 dB/year at ≥2 adjacent test locations in the same hemifield at P<0.01. Cox proportional hazard ratios (HR) were calculated to determine the predictive ability of baseline ONH and RNFL parameters for SAP progression using univariate and multivariate models. Seventy-three eyes of 73 patients (43 GS and 30 glaucoma, mean age 63.2±9.5 years) were enrolled (mean follow-up 51.5±11.3 months). Four of 43 GS (9.3%) and 6 of 30 (20%) glaucomatous eyes demonstrated progression. Mean time to progression was 50.8±11.4 months. Using multivariate models, abnormal CSLO temporal-inferior Moorfields classification (HR=3.76, 95% confidence interval (CI): 1.02-6.80, P=0.04), SLPECC inferior RNFLT (per -1 μm, HR=1.38, 95% CI: 1.02-2.2, P=0.02), and TDOCT inferior RNFLT (per -1 μm, HR=1.11, 95% CI: 1.04-1.2, P=0.001) had significant HRs for SAP progression. Abnormal baseline ONH topography and reduced inferior RNFL are predictive of SAP progression in GS and glaucomatous eyes.