Alberto Diniz-Filho

Optical Coherence Tomography Angiography Vessel Density in Healthy, Glaucoma Suspect, and Glaucoma Eyes

Purpose The purpose of this study was to compare retinal nerve fiber layer (RNFL) thickness and optical coherence tomography angiography (OCT-A) retinal vasculature measurements in healthy, glaucoma suspect, and glaucoma patients. Methods Two hundred sixty-one eyes of 164 healthy, glaucoma suspect, and open-angle glaucoma (OAG) participants from the Diagnostic Innovations in Glaucoma Study with good quality OCT-A images were included. Retinal vasculature information was summarized as a vessel density map and as vessel density (%), which is the proportion of flowing vessel area over the total area evaluated. Two vessel density measurements extracted from the RNFL were analyzed: (1) circumpapillary vessel density (cpVD) measured in a 750-μm-wide elliptical annulus around the disc and (2) whole image vessel density (wiVD) measured over the entire image. Areas under the receiver operating characteristic curves (AUROC) were used to evaluate diagnostic accuracy. Results Age-adjusted mean vessel density was significantly lower in OAG eyes compared with glaucoma suspects and healthy eyes. (cpVD: 55.1 ± 7%, 60.3 ± 5%, and 64.2 ± 3%, respectively; P < 0.001; and wiVD: 46.2 ± 6%, 51.3 ± 5%, and 56.6 ± 3%, respectively; P < 0.001). For differentiating between glaucoma and healthy eyes, the age-adjusted AUROC was highest for wiVD (0.94), followed by RNFL thickness (0.92) and cpVD (0.83). The AUROCs for differentiating between healthy and glaucoma suspect eyes were highest for wiVD (0.70), followed by cpVD (0.65) and RNFL thickness (0.65). Conclusions Optical coherence tomography angiography vessel density had similar diagnostic accuracy to RNFL thickness measurements for differentiating between healthy and glaucoma eyes. These results suggest that OCT-A measurements reflect damage to tissues relevant to the pathophysiology of OAG.

The Impact of Location of Progressive Visual Field Loss on Longitudinal Changes in Quality of Life of Patients with Glaucoma

PURPOSE To evaluate the association between rates of progressive loss in different regions of the visual field and longitudinal changes in quality of life (QoL). DESIGN Prospective, observational cohort study. PARTICIPANTS The study included 236 patients with glaucomatous visual field loss followed for an average of 4.3±1.5 years. METHODS All subjects had the 25-item National Eye Institute Visual Functioning 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 tests during follow-up. Evaluation of rates of visual field change was performed using 4 different regions (central inferior, central superior, peripheral inferior, and peripheral superior) of the integrated binocular visual field. The association between change in NEI VFQ-25 Rasch-calibrated scores and change in different regions of the visual field was investigated with a joint multivariable longitudinal linear mixed model. MAIN OUTCOME MEASURES The relationship between change in QoL scores and change of mean sensitivity in different regions of the visual field. RESULTS There was a significant correlation between change in the NEI VFQ-25 Rasch scores during follow-up and change in different regions of the visual field. Each 1 decibel (dB)/year change in binocular mean sensitivity of the central inferior area was associated with a decline of 2.6 units/year in the NEI VFQ-25 scores (R(2) = 35%; P < 0.001). Corresponding associations with change in QoL scores for the peripheral inferior, central superior, and peripheral superior areas of the visual field had R(2) values of 30%, 24%, and 19%, respectively. The association for the central inferior visual field area was statistically significantly stronger than those of the central superior area (P = 0.011) and peripheral superior area (P = 0.001), but not the peripheral inferior area (P = 0.171). Greater declines in NEI VFQ-25 scores were also seen in patients who had worse visual field sensitivity at baseline. CONCLUSIONS Progressive decline in sensitivity in the central inferior area of the visual field had the strongest association with longitudinal decline in QoL of patients with glaucoma.

Evaluation of Postural Control in Patients with Glaucoma Using a Virtual Reality Environment

PURPOSE To evaluate postural control using a dynamic virtual reality environment and the relationship between postural metrics and history of falls in patients with glaucoma. DESIGN Cross-sectional study. PARTICIPANTS The study involved 42 patients with glaucoma with repeatable visual field defects on standard automated perimetry (SAP) and 38 control healthy subjects. METHODS Patients underwent evaluation of postural stability by a force platform during presentation of static and dynamic visual stimuli on stereoscopic head-mounted goggles. The dynamic visual stimuli presented rotational and translational ecologically valid peripheral background perturbations. Postural stability was also tested in a completely dark field to assess somatosensory and vestibular contributions to postural control. History of falls was evaluated by a standard questionnaire. MAIN OUTCOME MEASURES Torque moments around the center of foot pressure on the force platform were measured, and the standard deviations of the torque moments (STD) were calculated as a measurement of postural stability and reported in Newton meters (Nm). The association with history of falls was investigated using Poisson regression models. Age, gender, body mass index, severity of visual field defect, best-corrected visual acuity, and STD on dark field condition were included as confounding factors. RESULTS Patients with glaucoma had larger overall STD than controls during both translational (5.12 ± 2.39 Nm vs. 3.85 ± 1.82 Nm, respectively; P = 0.005) and rotational stimuli (5.60 ± 3.82 Nm vs. 3.93 ± 2.07 Nm, respectively; P = 0.022). Postural metrics obtained during dynamic visual stimuli performed better in explaining history of falls compared with those obtained in static and dark field condition. In the multivariable model, STD values in the mediolateral direction during translational stimulus were significantly associated with a history of falls in patients with glaucoma (incidence rate ratio, 1.85; 95% confidence interval, 1.30-2.63; P = 0.001). CONCLUSIONS The study presented and validated a novel paradigm for evaluation of balance control in patients with glaucoma on the basis of the assessment of postural reactivity to dynamic visual stimuli using a virtual reality environment. The newly developed metrics were associated with a history of falls and may help to provide a better understanding of balance control in patients with glaucoma.

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

PURPOSE 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. DESIGN Prospective observational cohort study. PARTICIPANTS The study included 204 eyes of 102 patients with glaucomatous visual field defects on standard automated perimetry (SAP). METHODS 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. MAIN OUTCOME MEASURES The association between rates of change in binocular SAP MS and change in GDS questionnaire scores. RESULTS 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). CONCLUSIONS Faster visual field progression was associated with the occurrence of depressive symptoms in patients with glaucoma.

The Relative Odds of Progressing by Structural and Functional Tests in Glaucoma.

Purpose The purpose of this study was to evaluate the effect of disease severity and number of tests acquired during follow-up on the relative odds of identifying progression by structural or functional tests in glaucoma. Methods This was an observational cohort study involving 462 eyes of 305 patients with glaucoma and 62 eyes of 49 healthy subjects. Glaucoma patients and healthy subjects were followed for an average of 3.6 ± 0.9 and 3.8 ± 0.9 years, with a median (interquantile range) of 8 (6–9) and 7 (6–8) visits, respectively. At each visit, subjects underwent visual field assessment with standard automated perimetry (SAP) and retinal nerve fiber layer (RNFL) evaluation by spectral-domain optical coherence tomography (SD-OCT). Slopes of change in SAP mean sensitivity and OCT RNFL thickness over time were estimated by linear regression using progressively cumulative visits over time. Cutoff values for age-related expected rates of change for each test were obtained from the healthy group. Progression by SD-OCT and/or SAP was determined if the slope of change was statistically significant and also lower (faster) than the fifth percentile cutoff calculated from the healthy group. A generalized estimating equation logistic regression model was used to evaluate the relative odds of progressing by OCT versus SAP in glaucoma eyes. Results Eyes with less severe disease at baseline had a higher chance of being detected as progressing by SD-OCT but not by SAP, whereas an increase in disease severity at baseline increased the chance that the eye would be detected as progressing by SAP but not SD-OCT. Each 1 dB higher MD was associated with a 5% increase in the odds of detecting progression by SD-OCT versus SAP (odds ratio = 1.05 per 1 dB; 95% confidence interval: 1.01–1.09; P = 0.005). Conclusions The ability to detect glaucoma progression by SAP versus SD-OCT is significantly influenced by the stage of disease. Our results may provide useful information for guiding clinicians on the relative utility of these tests for detecting change throughout the disease continuum.

Predicting Risk of Motor Vehicle Collisions in Patients with Glaucoma: A Longitudinal Study

Purpose To evaluate the ability of longitudinal Useful Field of View (UFOV) and simulated driving measurements to predict future occurrence of motor vehicle collision (MVC) in drivers with glaucoma. Design Prospective observational cohort study. Participants 117 drivers with glaucoma followed for an average of 2.1 ± 0.5 years. Methods All subjects had standard automated perimetry (SAP), UFOV, driving simulator, and cognitive assessment obtained at baseline and every 6 months during follow-up. The driving simulator evaluated reaction times to high and low contrast peripheral divided attention stimuli presented while negotiating a winding country road, with central driving task performance assessed as “curve coherence”. Drivers with MVC during follow-up were identified from Department of Motor Vehicle records. Main Outcome Measures Survival models were used to evaluate the ability of driving simulator and UFOV to predict MVC over time, adjusting for potential confounding factors. Results Mean age at baseline was 64.5 ± 12.6 years. 11 of 117 (9.4%) drivers had a MVC during follow-up. In the multivariable models, low contrast reaction time was significantly predictive of MVC, with a hazard ratio (HR) of 2.19 per 1 SD slower reaction time (95% CI, 1.30 to 3.69; P = 0.003). UFOV divided attention was also significantly predictive of MVC with a HR of 1.98 per 1 SD worse (95% CI, 1.10 to 3.57; P = 0.022). Global SAP visual field indices in the better or worse eye were not predictive of MVC. The longitudinal model including driving simulator performance was a better predictor of MVC compared to UFOV (R2 = 0.41 vs R2 = 0.18). Conclusions Longitudinal divided attention metrics on the UFOV test and during simulated driving were significantly predictive of risk of MVC in glaucoma patients. These findings may help improve the understanding of factors associated with driving impairment related to glaucoma.

Frequency Doubling Technology Perimetry and Changes in Quality of Life of Glaucoma Patients: A Longitudinal Study

PURPOSE To evaluate the relationship between rates of change on frequency doubling technology (FDT) perimetry and longitudinal changes in quality of life (QoL) of glaucoma patients. DESIGN Prospective observational cohort study. METHODS One hundred fifty-two subjects (127 glaucoma and 25 healthy) were followed for an average of 3.2 ± 1.1 years. All subjects were evaluated with National Eye Institute Visual Function Questionnaire (NEI VFQ-25), FDT, and standard automated perimetry (SAP). Glaucoma patients had a median of 3 NEI VFQ-25, 8 FDT, and 8 SAP tests during follow-up. Mean sensitivities of the integrated binocular visual fields were estimated for FDT and SAP and used to calculate rates of change. A joint longitudinal multivariable mixed model was used to investigate the association between change in binocular mean sensitivities and change in NEI VFQ-25 Rasch-calibrated scores. RESULTS There was a statistically significant correlation between change in binocular mean sensitivity for FDT and change in NEI VFQ-25 scores during follow-up in the glaucoma group. In multivariable analysis with the confounding factors, each 1 dB/year change in binocular FDT mean sensitivity corresponded to a change of 0.8 units per year in the NEI VFQ-25 scores (P = .001). For binocular SAP mean sensitivity, each 1 dB/year change was associated with 2.4 units per year change in NEI VFQ-25 scores (P < .001). The multivariable model containing baseline and rate of change information from SAP had stronger ability to predict change in NEI VFQ-25 scores compared to the equivalent model for FDT (R(2) of 50% and 30%, respectively; P = .001). CONCLUSION SAP performed significantly better than FDT in predicting change in NEI VFQ-25 scores in our population, suggesting that it may still be the preferable perimetric technique for predicting risk of disability from the disease.

Association of Fast Visual Field Loss With Risk of Falling in Patients With Glaucoma

IMPORTANCE Patients with glaucoma and a history of fast visual field loss might be at an increased risk for falls compared with those with a history of slow visual field loss, but, to date, this association has not been previously investigated in the literature. OBJECTIVE To evaluate the association between self-reported falls and past rate of visual field loss in a cohort of patients with glaucoma followed up over time. DESIGN, SETTING, AND PARTICIPANTS This observational cohort study included patients diagnosed as having glaucoma who had been followed up at the Visual Performance Laboratory, University of California, San Diego, at 6-month intervals for a mean (SD) of 7.5 (2.6) years from January 1, 2005, through December 31, 2015. Self-reported number of falls during the past year was obtained at the last follow-up visit. Integrated binocular fields were estimated from the monocular fields. Linear mixed models were used to calculate rates of change in binocular mean sensitivity over time. Poisson models were used to evaluate the association between the self-reported number of falls and rates of visual field loss. The models adjusted for the current level of visual field damage and other confounding variables. MAIN OUTCOMES AND MEASURES Association between rates of binocular visual field loss and self-reported number of falls. RESULTS The study included 116 patients with glaucoma with a mean (SD) age of 73.1 (10.7) years (55 women [47.4%], 84 white individuals [72.4%], and 32 black individuals [27.6%]). Of the 116 patients, 29 (25.0%) reported at least 1 fall in the previous year. The mean rate of change in binocular mean sensitivity was faster for patients who reported a history of falls vs those who did not (-0.36 vs -0.17 dB/y; mean difference, 0.20 dB/y; 95% CI, 0.09-0.31 dB/y; P < .001). History of fast visual field loss was significantly associated with falls (rate ratio, 2.28 per 0.5 dB/y faster; 95% CI, 1.15-4.52 db/y; P = .02), even after adjusting for confounding factors. CONCLUSIONS AND RELEVANCE The rate of visual field loss was associated with a self-reported history of falls in the past year even after taking into account the magnitude of visual field defect. However, although a positive association was found, further studies are necessary to establish whether a cause-and-effect relationship exists between rate of visual field loss and self-reported history of falls.

Lamina Cribrosa in Glaucoma: Diagnosis and Monitoring

The lamina cribrosa is the putative site of retinal ganglion cell axonal injury in glaucoma. Although histological studies have provided evidence of structural changes to the lamina cribrosa, even in early stages of glaucoma, until recently, the ability to evaluate the lamina cribrosa in vivo has been limited. Recent advances in optical coherence tomography, including enhanced depth and swept-source imaging, have changed this, providing a means to image the lamina cribrosa. Imaging has identified general and localized configurational changes in the lamina of glaucomatous eyes, including posterior laminar displacement, altered laminar thickness, and focal laminar defects with spatial association with conventional structural and functional losses. In addition, although the temporal relationship between changes to the lamina cribrosa and glaucomatous retinal ganglion cell loss is yet to be elucidated, quantitative measurements of laminar microarchitecture have good reproducibility and offer the potential to serve as biomarkers for glaucoma diagnosis and progression.

A Portable Platform for Evaluation of Visual Performance in Glaucoma Patients

Purpose To propose a new tablet-enabled test for evaluation of visual performance in glaucoma, the PERformance CEntered Portable Test (PERCEPT), and to evaluate its ability to predict history of falls and motor vehicle crashes. Design Cross-sectional study. Methods The study involved 71 patients with glaucomatous visual field defects on standard automated perimetry (SAP) and 59 control subjects. The PERCEPT was based on the concept of increasing visual task difficulty to improve detection of central visual field losses in glaucoma patients. Subjects had to perform a foveal 8-alternative-forced-choice orientation discrimination task, while detecting a simultaneously presented peripheral stimulus within a limited presentation time. Subjects also underwent testing with the Useful Field of View (UFOV) divided attention test. The ability to predict history of motor vehicle crashes and falls was investigated by odds ratios and incident-rate ratios, respectively. Results When adjusted for age, only the PERCEPT processing speed parameter showed significantly larger values in glaucoma compared to controls (difference: 243ms; P<0.001). PERCEPT results had a stronger association with history of motor vehicle crashes and falls than UFOV. Each 1 standard deviation increase in PERCEPT processing speed was associated with an odds ratio of 2.69 (P = 0.003) for predicting history of motor vehicle crashes and with an incident-rate ratio of 1.95 (P = 0.003) for predicting history of falls. Conclusion A portable platform for testing visual function was able to detect functional deficits in glaucoma, and its results were significantly associated with history of involvement in motor vehicle crashes and history of falls.