Carolina P. B. Gracitelli

Association Between Progressive Retinal Nerve Fiber Layer Loss and Longitudinal Change in Quality of Life in Glaucoma

IMPORTANCE 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. OBJECTIVE To evaluate the relationship between rates of retinal nerve fiber layer (RNFL) loss and longitudinal changes in quality of life in glaucoma. DESIGN, SETTING, AND PARTICIPANTS 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. MAIN OUTCOMES AND MEASURES Association between change in binocular RNFL thickness (RNFL thickness in the better eye at each point) and change in NEI VFQ-25 scores. RESULTS 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. CONCLUSIONS AND RELEVANCE 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.

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.

Estimated Rates of Retinal Ganglion Cell Loss in Glaucomatous Eyes with and without Optic Disc Hemorrhages

Purpose To evaluate whether optic disc hemorrhages are associated with faster rates of estimated retinal ganglion cell (RGC) loss in glaucoma. Methods A longitudinal observational cohort study of 222 eyes of 122 patients with glaucoma recruited from the Diagnostic Innovations Glaucoma Study (DIGS) followed for an average of 3.74±0.85 years. All subjects had optical coherence tomography and standard automated perimetry during follow up. Optic disc hemorrhages were detected by masked evaluation of stereophotographs. Rates of change in estimated numbers of RGCs were determined using a previously described method. A random coefficients model was used to investigate the relationship between disc hemorrhages and rates of change in estimated RGC counts over time. Results 19 eyes of 18 subjects had at least one disc hemorrhage during follow up. At baseline, average estimated RGC counts in eyes with and without disc hemorrhages were 677,994 cells and 682,021 cells, respectively (P = 0.929). Eyes with optic disc hemorrhages during follow-up had significantly faster rates of estimated RGC loss than eyes without disc hemorrhages (22,233 cells/year versus 10,704 cells/year, P = 0.020). The effect of disc hemorrhages on the rates of estimated RGC loss remained significant after adjusting for confounding variables. Conclusion Eyes with disc hemorrhages showed faster rates of RGC loss compared to eyes without disc hemorrhages. These results provide further evidence that disc hemorrhages should be considered as an indicator of increased risk for faster neural loss in 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.

Spectral-Domain Optical Coherence Tomography for Glaucoma Diagnosis

Identification of structural damage to the optic nerve and retinal nerve fiber layer (RNFL) is an essential component of diagnosis and management of glaucoma. The introduction of spectral-domain OCT (SD-OCT) has allowed objective quantification of damage to these structures with unprecedented resolution. In addition, recent attention has been directed towards imaging the macular area for quantifying loss of neural tissue caused by the disease. Many studies have evaluated and compared the diagnostic accuracies of a variety of parameters that can be obtained from imaging these areas of the ocular fundus. In this article, we critically review the existing literature evaluating the diagnostic accuracy of SD-OCT in glaucoma and we discuss issues related to how SD-OCT results should be incorporated into clinical practice.

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.

The Use of Spectral-Domain Optical Coherence Tomography to Detect Glaucoma Progression

Detection of progression and measurement of rates of change is at the core of glaucoma management, and the use of Spectral Domain Optical Coherence Tomography (SD-OCT) has significantly improved our ability to evaluate change in the disease. In this review, we critically assess the existing literature on the use of SD-OCT for detecting glaucoma progression and estimating rates of change. We discuss aspects related to the reproducibility of measurements, their accuracy to detect longitudinal change over time, and the effect of aging on the ability to detect progression. In addition, we discuss recent studies evaluating the use of combined structure and function approaches to improve detection of glaucoma progression.

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.