Fábio B. Daga

Association Between Neurocognitive Decline and Visual Field Variability in Glaucoma

Importance Visual field variability may impair detection of glaucoma progression over time. Despite the possible overlap between neurocognitive disorders and glaucoma in older individuals, no study has investigated the association between cognitive changes and visual field variability. Objective To evaluate the association between global neurocognitive impairment and visual field variability in patients diagnosed as having glaucoma or glaucoma suspects. Design, Setting, and Participants This prospective observational cohort study was conducted at the Visual Performance Laboratory, University of California, San Diego. The study involved 211 eyes of 115 patients followed up for a mean (SD) period of 2.5 (0.8) years, ranging from 1.2 to 4.7 years. Data were obtained during the period extending from March 2011 to April 2015, with data analysis conducted from November 2015 to May 2016. Main Outcomes and Measures Association between cognitive decline and visual field variability. Patients were monitored with standard automated perimetry (SAP) and had longitudinal assessment of cognitive ability using the Montreal Cognitive Assessment (MoCA). Visual field variability was estimated by the SD of the residuals of ordinary least squares linear regressions of SAP mean deviation (MD) values over time. Linear regression models were used to investigate the association between cognitive decline and visual field variability, adjusting for potentially confounding factors. Results Among the 115 patients, the mean (SD) age at baseline was 67.4 (10.1) years, 63 were men (54.8%), and 86 were white (74.8%). There was a statistically significant association between change in MoCA scores and visual field variability over time. In a univariable model, a 5-point decline in MoCA score was associated with an increase of 0.18 dB in the SD of residuals of SAP MD (R2 = 4.3%; 95% CI, 0.06-0.30; P = .003). In a multivariable model adjusting for baseline MoCA score, mean SAP MD, age, sex, race/ethnicity, educational level, income, and number of SAP tests, each 5-point decline in MoCA score was associated with an increase of 0.23 dB in the SD of residuals of SAP MD (95% CI, 0.11-0.35; P < .001). Conclusions and Relevance Cognitive decline was associated with increased visual field variability during follow-up. These findings suggest that screening and monitoring of cognitive dysfunction may be important in the assessment of visual field progression in the context of glaucoma.

Detecting Glaucoma With a Portable Brain-Computer Interface for Objective Assessment of Visual Function Loss.

Importance The current assessment of visual field loss in diseases such as glaucoma is affected by the subjectivity of patient responses and the lack of portability of standard perimeters. Objective To describe the development and initial validation of a portable brain-computer interface (BCI) for objectively assessing visual function loss. Design, Setting, and Participants This case-control study involved 62 eyes of 33 patients with glaucoma and 30 eyes of 17 healthy participants. Glaucoma was diagnosed based on a masked grading of optic disc stereophotographs. All participants underwent testing with a BCI device and standard automated perimetry (SAP) within 3 months. The BCI device integrates wearable, wireless, dry electroencephalogram and electrooculogram systems and a cellphone-based head-mounted display to enable the detection of multifocal steady state visual-evoked potentials associated with visual field stimulation. The performances of global and sectoral multifocal steady state visual-evoked potentials metrics to discriminate glaucomatous from healthy eyes were compared with global and sectoral SAP parameters. The repeatability of the BCI device measurements was assessed by collecting results of repeated testing in 20 eyes of 10 participants with glaucoma for 3 sessions of measurements separated by weekly intervals. Main Outcomes and Measures Receiver operating characteristic curves summarizing diagnostic accuracy. Intraclass correlation coefficients and coefficients of variation for assessing repeatability. Results Among the 33 participants with glaucoma, 19 (58%) were white, 12 (36%) were black, and 2 (6%) were Asian, while among the 17 participants with healthy eyes, 9 (53%) were white, 8 (47%) were black, and none were Asian. The receiver operating characteristic curve area for the global BCI multifocal steady state visual-evoked potentials parameter was 0.92 (95% CI, 0.86-0.96), which was larger than for SAP mean deviation (area under the curve, 0.81; 95% CI, 0.72-0.90), SAP mean sensitivity (area under the curve, 0.80; 95% CI, 0.69-0.88; P = .03), and SAP pattern standard deviation (area under the curve, 0.77; 95% CI, 0.66-0.87; P = .01). No statistically significant differences were seen for the sectoral measurements between the BCI and SAP. Intraclass coefficients for global and sectoral parameters ranged from 0.74 to 0.92, and mean coefficients of variation ranged from 3.03% to 7.45%. Conclusions and Relevance The BCI device may be useful for assessing the electrical brain responses associated with visual field stimulation. The device discriminated eyes with glaucomatous neuropathy from healthy eyes in a clinically based setting. Further studies should investigate the feasibility of the BCI device for home-based testing as well as for detecting visual function loss over time.

Wayfinding and Glaucoma: A Virtual Reality Experiment

Purpose Wayfinding, the process of determining and following a route between an origin and a destination, is an integral part of everyday tasks. The purpose of this study was to investigate the impact of glaucomatous visual field loss on wayfinding behavior using an immersive virtual reality (VR) environment. Methods This cross-sectional study included 31 glaucomatous patients and 20 healthy subjects without evidence of overall cognitive impairment. Wayfinding experiments were modeled after the Morris water maze navigation task and conducted in an immersive VR environment. Two rooms were built varying only in the complexity of the visual scene in order to promote allocentric-based (room A, with multiple visual cues) versus egocentric-based (room B, with single visual cue) spatial representations of the environment. Wayfinding tasks in each room consisted of revisiting previously visible targets that subsequently became invisible. Results For room A, glaucoma patients spent on average 35.0 seconds to perform the wayfinding task, whereas healthy subjects spent an average of 24.4 seconds (P = 0.001). For room B, no statistically significant difference was seen on average time to complete the task (26.2 seconds versus 23.4 seconds, respectively; P = 0.514). For room A, each 1-dB worse binocular mean sensitivity was associated with 3.4% (P = 0.001) increase in time to complete the task. Conclusions Glaucoma patients performed significantly worse on allocentric-based wayfinding tasks conducted in a VR environment, suggesting visual field loss may affect the construction of spatial cognitive maps relevant to successful wayfinding. VR environments may represent a useful approach for assessing functional vision endpoints for clinical trials of emerging therapies in ophthalmology.

What Is the Amount of Visual Field Loss Associated With Disability in Glaucoma

PURPOSE To propose a new methodology for classifying patient-reported outcomes in glaucoma and for quantifying the amount of visual field damage associated with disability in the disease. DESIGN Cross-sectional study. METHODS A total of 263 patients with glaucoma were included. Vision-related disability was assessed by the National Eye Institute Visual Function Questionnaire (NEI VFQ-25). A latent class analysis (LCA) model was applied to analyze NEI VFQ-25 data and patients were divided into mutually exclusive classes according to their responses to the questionnaires. Differences in standard automated perimetry (SAP) mean deviation (MD) and integrated binocular mean sensitivity (MS) values between classes were investigated. The optimal number of classes was defined based on goodness-of-fit criteria, interpretability, and clinical utility. RESULTS The model with 2 classes, disabled and nondisabled, had the best fit with an entropy of 0.965, indicating excellent separation of classes. The disabled group had 48 (18%) patients, whereas 215 (82%) patients were classified as nondisabled. The average MD of the better eye in the disabled group was -5.98 dB vs -2.51 dB in the nondisabled group (P < .001). For the worse eye, corresponding values were -13.36 dB and -6.05 dB, respectively (P < .001). CONCLUSION Application of an LCA model allowed categorization of patient-reported outcomes and quantification of visual field levels associated with disability in glaucoma. A damage of approximately -6 dB for SAP MD, indicating relatively early visual field loss, may already be associated with significant disability if occurring in the better eye.

Is vision-related quality of life impaired in patients with preperimetric glaucoma?

Background/aims To investigate whether subjects with preperimetric glaucoma exhibit decline in patient-reported vision-related quality of life (QoL) compared with healthy individuals. Methods This cross-sectional study included 45 patients with preperimetric glaucoma, 102 patients with perimetric glaucoma and 81 healthy controls. Perimetric glaucoma was defined by the presence of repeatable abnormal standard automated perimetry tests and corresponding optic nerve damage in at least one eye. Preperimetric glaucoma was defined based on the presence of retinal nerve fibre layer (RNFL) loss as detected by spectral-domain optical coherence tomography in the absence of visual field loss. Patient-reported QoL was measured by the 25-item National Eye Institute Visual Function Questionnaire (NEI VFQ-25). Results Patients with preperimetric glaucoma had significantly thinner average RNFL in the better eye compared with controls (79.9±9.2 µm vs 97.8±8.6 µm; p<0.001). There was no significant difference in Rasch-calibrated NEI VFQ-25 scores between the preperimetric and control groups (72.8±16.8 vs 73.7±20.2, respectively; p=0.964). The average NEI VFQ-25 score in the perimetric glaucoma group was 58.9±18.6 and was significantly different than the average score in the preperimetric glaucoma and healthy groups (p<0.001 for both comparisons). Conclusion Contrary to patients with perimetric damage, preperimetric glaucoma does not seem to be associated with loss in QoL. Prevention of disability from glaucoma may benefit from early diagnosis during a ‘window of opportunity’ given by detecting structural loss before visual field damage.

Fear of falling and postural reactivity in patients with glaucoma

Purpose To investigate the relationship between postural metrics obtained by dynamic visual stimulation in a virtual reality environment and the presence of fear of falling in glaucoma patients. Methods This cross-sectional study included 35 glaucoma patients and 26 controls that underwent evaluation of postural balance by a force platform during presentation of static and dynamic visual stimuli with head-mounted goggles (Oculus Rift). In dynamic condition, a peripheral translational stimulus was used to induce vection and assess postural reactivity. Standard deviations of torque moments (SDTM) were calculated as indicative of postural stability. Fear of falling was assessed by a standardized questionnaire. The relationship between a summary score of fear of falling and postural metrics was investigated using linear regression models, adjusting for potentially confounding factors. Results Subjects with glaucoma reported greater fear of falling compared to controls (-0.21 vs. 0.27; P = 0.039). In glaucoma patients, postural metrics during dynamic visual stimulus were more associated with fear of falling (R2 = 18.8%; P = 0.001) than static (R2 = 3.0%; P = 0.005) and dark field (R2 = 5.7%; P = 0.007) conditions. In the univariable model, fear of falling was not significantly associated with binocular standard perimetry mean sensitivity (P = 0.855). In the multivariable model, each 1 Nm larger SDTM in anteroposterior direction during dynamic stimulus was associated with a worsening of 0.42 units in the fear of falling questionnaire score (P = 0.001). Conclusion In glaucoma patients, postural reactivity to a dynamic visual stimulus using a virtual reality environment was more strongly associated with fear of falling than visual field testing and traditional balance assessment.