Deep Learning-Assisted Detection of Glaucoma Progression in Spectral-Domain OCT.

PURPOSE: To develop and validate a deep learning (DL) model for detection of glaucoma progression using spectral-domain (SD)-OCT measurements of retinal nerve fiber layer (RNFL) thickness. DESIGN: Retrospective cohort study. PARTICIPANTS: A total of 14 034 SD-OCT scans from 816 eyes from 462 individuals. METHODS: A DL convolutional neural network was trained to assess SD-OCT RNFL thickness measurements of 2 visits (a baseline and a follow-up visit) along with time between visits to predict the probability of glaucoma progression. The ground truth was defined by consensus from subjective grading by glaucoma specialists. Diagnostic performance was summarized by the area under the receiver operator characteristic curve (AUC), sensitivity, and specificity, and was compared with conventional trend-based analyses of change. Interval likelihood ratios were calculated to determine the impact of DL model results in changing the post-test probability of progression. MAIN OUTCOME MEASURES: The AUC, sensitivity, and specificity of the DL model. RESULTS: The DL model had an AUC of 0.938 (95% confidence interval [CI], 0.921-0.955), with sensitivity of 87.3% (95% CI, 83.6%-91.6%) and specificity of 86.4% (95% CI, 79.9%-89.6%). When matched for the same specificity, the DL model significantly outperformed trend-based analyses. Likelihood ratios for the DL model were associated with large changes in the probability of progression in the vast majority of SD-OCT tests. CONCLUSIONS: A DL model was able to assess the probability of glaucomatous structural progression from SD-OCT RNFL thickness measurements. The model agreed well with expert judgments and outperformed conventional trend-based analyses of change, while also providing indication of the likely locations of change. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

Blood Pressure and Glaucomatous Progression in a Large Clinical Population.

PURPOSE: To investigate the effect of systemic arterial blood pressure (BP) on rates of progressive structural damage over time in glaucoma. DESIGN: Retrospective cohort study. PARTICIPANTS: A total of 7501 eyes of 3976 subjects with glaucoma or suspected of glaucoma followed over time from the Duke Glaucoma Registry. METHODS: Linear mixed models were used to investigate the effects of BP on the rates of retinal nerve fiber layer (RNFL) loss from spectral-domain OCT (SD-OCT) over time. Models were adjusted for intraocular pressure (IOP), gender, race, diagnosis, central corneal thickness (CCT), follow-up time, and baseline disease severity. MAIN OUTCOME MEASURE: Effect of mean arterial pressure (MAP), systolic arterial pressure (SAP), and diastolic arterial pressure (DAP) on rates of RNFL loss over time. RESULTS: A total of 157 291 BP visits, 45 408 IOP visits, and 30 238 SD-OCT visits were included. Mean rate of RNFL change was -0.70 µm/year (95% confidence interval, -0.72 to -0.67 µm/year). In univariable models, MAP, SAP, and DAP during follow-up were not significantly associated with rates of RNFL loss. However, when adjusted for mean IOP during follow-up, each 10 mmHg reduction in mean MAP (-0.06 µm/year; P = 0.007) and mean DAP (-0.08 µm/year; P < 0.001) but not SAP (-0.01 µm/year; P = 0.355) was associated with significantly faster rates of RNFL thickness change over time. The effect of the arterial pressure metrics remained significant after additional adjustment for baseline age, diagnosis, sex, race, follow-up time, disease severity, and corneal thickness. CONCLUSIONS: When adjusted for IOP, lower MAP and DAP during follow-up were significantly associated with faster rates of RNFL loss, suggesting that levels of systemic BP may be a significant factor in glaucoma progression.

Impact of Intraocular Pressure Control on Rates of Retinal Nerve Fiber Layer Loss in a Large Clinical Population.

PURPOSE: To investigate the impact of intraocular pressure (IOP) control on rates of change of spectral-domain OCT (SD-OCT) retinal nerve fiber layer (RNFL) thickness in a large clinical population. DESIGN: Retrospective cohort study. PARTICIPANTS: A total of 85 835 IOP measurements and 60 223 SD-OCT tests from 14 790 eyes of 7844 patients. METHODS: Data were extracted from the Duke Glaucoma Registry, a large database of electronic medical records of patients with glaucoma and suspected disease followed over time at the Duke Eye Center and satellite clinics. All records from patients with a minimum of 6 months of follow-up and at least 2 good-quality SD-OCT scans and 2 clinical visits with Goldmann applanation tonometry were included. Eyes were categorized according to the frequency of visits with IOP below cutoffs of 21 mmHg, 18 mmHg, and 15 mmHg over time. Rates of change for global RNFL thickness were obtained using linear mixed models and classified as slow if change was slower than -1.0 µm/year; moderate if between -1.0 and -2.0 µm/year; and fast if faster than -2.0 µm/year. Multivariable models were adjusted for age, gender, race, diagnosis, central corneal thickness, follow-up time, and baseline disease severity. MAIN OUTCOME MEASURES: Rates of change in SD-OCT RNFL thickness according to levels of IOP control. RESULTS: Eyes had a mean follow-up of 3.5±1.9 years. Average rate of change in RNFL thickness was -0.68±0.59 µm/year. Each 1 mmHg higher mean IOP was associated with 0.05 µm/year faster RNFL loss (P < 0.001) after adjustment for potentially confounding variables. For eyes that had fast progression, 41% of them had IOP <21 mmHg in all visits during follow-up, whereas 20% of them had all visits with IOP <18 mmHg, but only 9% of them had all visits with IOP <15 mmHg. CONCLUSIONS: Intraocular pressure was significantly associated with rates of progressive RNFL loss in a large clinical population. Eyes with stricter IOP control over follow-up visits had a smaller chance of exhibiting fast deterioration. Our findings may assist clinicians in establishing target pressures in clinical practice.

Human Versus Machine: Comparing a Deep Learning Algorithm to Human Gradings for Detecting Glaucoma on Fundus Photographs.

PURPOSE: To compare the diagnostic performance of human gradings vs predictions provided by a machine-to-machine (M2M) deep learning (DL) algorithm trained to quantify retinal nerve fiber layer (RNFL) damage on fundus photographs. DESIGN: Evaluation of a machine learning algorithm. METHODS: An M2M DL algorithm trained with RNFL thickness parameters from spectral-domain optical coherence tomography was applied to a subset of 490 fundus photos of 490 eyes of 370 subjects graded by 2 glaucoma specialists for the probability of glaucomatous optical neuropathy (GON), and estimates of cup-to-disc (C/D) ratios. Spearman correlations with standard automated perimetry (SAP) global indices were compared between the human gradings vs the M2M DL-predicted RNFL thickness values. The area under the receiver operating characteristic curves (AUC) and partial AUC for the region of clinically meaningful specificity (85%-100%) were used to compare the ability of each output to discriminate eyes with repeatable glaucomatous SAP defects vs eyes with normal fields. RESULTS: The M2M DL-predicted RNFL thickness had a significantly stronger absolute correlation with SAP mean deviation (rho=0.54) than the probability of GON given by human graders (rho=0.48; P < .001). The partial AUC for the M2M DL algorithm was significantly higher than that for the probability of GON by human graders (partial AUC = 0.529 vs 0.411, respectively; P = .016). CONCLUSION: An M2M DL algorithm performed as well as, if not better than, human graders at detecting eyes with repeatable glaucomatous visual field loss. This DL algorithm could potentially replace human graders in population screening efforts for glaucoma.

Psychometric properties of the Portuguese version of the National Eye Institute Visual Function Questionnaire-25.

BACKGROUND: To investigate the psychometric properties of the Brazilian Portuguese version of the National Eye Institute Visual Function Questionnaire (NEI VFQ-25) questionnaire in a group of patients with different eye diseases. METHODS: Cross-sectional study. All subjects completed the Portuguese version of the NEI VFQ-25 questionnaire. Another questionnaire containing a survey about clinical and demographics data was also applied. Rasch analysis was used to evaluate the psychometric properties of the NEI VFQ-25. RESULTS: The study included 104 patients with cataract, 65 with glaucoma and 83 with age macular degeneration. Mean age was 70.7 ± 9.9 years, with 143 female (56.7%) and 109 male patients (43.2%). Mean visual acuity was 0.47 and 1.17 logMAR in the better and worse eye, respectively. According to Rasch analysis, seven items were found to misfit. Those items belonged to the following subscales: general health, social function, mental health, ocular pain and role limitations. The principal component analysis of the residuals showed that 55.5% of the variance was explained by the principal component. Eight items loaded positively onto the first contrast with a correlation higher than 0.4. These items belonged to the following subscales: near vision, distance vision, mental health and dependency. After excluding those items, we were able to isolate items from the NEI VFQ-25, related only to a visual functioning component. Finally, the principal component analysis from residuals of this revised version of the NEI VFQ-25 (items related to visual function) showed that the principal component explained 61.2% of the variance, showing no evidence of multidimensionality. CONCLUSIONS: The Portuguese version of the NEI VFQ-25 is not a unidimensional instrument. We were able to find items that belong to a different trait, possible related to a socio-emotional component. Thus, in order to obtain psychometrically valid constructs, both the visual functioning and socio-emotional components should be analyzed separately.

Assessing driving risk in patients with glaucoma / Avaliação do risco de dirigir em pacientes com glaucoma

ABSTRACT Glaucoma is the leading cause of irreversible blindness worldwide and can affect a broad array of daily activities, including driving. Recently, studies investigating the relationship between driving performance and glaucoma have received a great deal of interest. Assessment of driving behavior is not straightforward because driving is a complex skill involving significant multi-tasking ability. In this review, we summarize recent work from clinical studies investigating how glaucoma can affect driving performance. Patients with glaucoma are more likely to be involved in motor vehicle collisions when compared to healthy subjects. Here we describe how conventional functional tests performed in glaucoma patients, such as visual field measurements via standard automatic perimetry, are associated with driving performance. However, the risk of motor vehicle collisions is not entirely attributable to visual field impairment in glaucoma, suggesting that other factors also account for both driving safety and performance. Finally, we show different studies suggesting that parameters from driving simulators can be helpful because they can identify the impact of visual loss on complex situations.

RESUMO O glaucoma é a principal causa de cegueira irreversível em todo o mundo e pode afetar uma ampla gama de atividades diárias, incluindo a direção veicular. Recentemente, estudos que investigam a relação entre o desempenho na condução veicular e o glaucoma têm recebido grande interesse. A avaliação do comportamento de dirigir não é direta porque dirigir é uma habilidade complexa que envolve habilidade multitarefa significativa. Nesta revisão, resumimos trabalhos recentes de estudos clínicos que investigam como o glaucoma pode afetar o desempenho na direção. Pacientes com glaucoma têm maior probabilidade de se envolverem em colisões de veículos motorizados quando comparados a indivíduos saudáveis. Descrevemos aqui como os testes funcionais convencionais realizados em pacientes com glaucoma, como as medições de campo visual por meio de perimetria automática padrão, estão associados ao desempenho na direção. No entanto, o risco de colisão de veículo motorizado não é totalmente atribuível ao comprometimento do campo visual no glaucoma, sugerindo que outros fatores também são responsáveis pela segurança e pelo desempenho. Finalmente, mostramos diferentes estudos sugerindo que os parâmetros dos simuladores de direção podem ser úteis porque eles podem identificar o impacto da perda visual em situações de complexas.

Assessing driving risk in patients with glaucoma.

Glaucoma is the leading cause of irreversible blindness worldwide and can affect a broad array of daily activities, including driving. Recently, studies investigating the relationship between driving performance and glaucoma have received a great deal of interest. Assessment of driving behavior is not straightforward because driving is a complex skill involving significant multi-tasking ability. In this review, we summarize recent work from clinical studies investigating how glaucoma can affect driving performance. Patients with glaucoma are more likely to be involved in motor vehicle collisions when compared to healthy subjects. Here we describe how conventional functional tests performed in glaucoma patients, such as visual field measurements via standard automatic perimetry, are associated with driving performance. However, the risk of motor vehicle collisions is not entirely attributable to visual field impairment in glaucoma, suggesting that other factors also account for both driving safety and performance. Finally, we show different studies suggesting that parameters from driving simulators can be helpful because they can identify the impact of visual loss on complex situations.

Association between Rates of Visual Field Progression and Intraocular Pressure Measurements Obtained by Different Tonometers.

PURPOSE: To investigate the associations between intraocular pressure (IOP) measurements obtained by different tonometric methods and rates of visual field loss in a cohort of patients with glaucoma followed over time. DESIGN: Prospective, observational cohort study. PARTICIPANTS: This study included 213 eyes of 125 glaucomatous patients who were followed for an average of 2.4±0.6 years. METHODS: At each visit, IOP measurements were obtained using Goldmann applanation tonometry (GAT), the Ocular Response Analyzer (ORA) (Reichert, Inc., Depew, NY), corneal-compensated IOP (IOPcc), and the ICare Rebound Tonometer (RBT) (Tiolat, Oy, Helsinki, Finland). Rates of visual field loss were assessed by standard automated perimetry (SAP) mean deviation (MD). Linear mixed models were used to investigate the relationship between mean IOP by each tonometer and rates of visual field loss over time, while adjusting for age, race, central corneal thickness, and corneal hysteresis. MAIN OUTCOME MEASURES: Strength of associations (R2) between IOP measurements from each tonometer and rates of SAP MD change over time. RESULTS: Average values for mean IOP over time measured by GAT, ORA, and RBT were 14.4±3.3, 15.2±4.2, and 13.4±4.2 mmHg, respectively. Mean IOPcc had the strongest relationship with SAP MD loss over time (R2 = 24.5%) and was significantly different from the models using mean GAT IOP (R2 = 11.1%; 95% confidence interval [CI] of the difference, 6.6-19.6) and mean RBT IOP (R2= 5.8%; 95% CI of the difference, 11.1-25.0). CONCLUSIONS: Mean ORA IOPcc was more predictive of rates of visual field loss than mean IOP obtained by GAT or RBT. By correcting for corneal-induced artifacts, IOPcc measurements may present significant advantages for predicting clinically relevant outcomes in patients with glaucoma.

Predicting Vision-Related Disability in Glaucoma.

PURPOSE: To present a new methodology for investigating predictive factors associated with development of vision-related disability in glaucoma. DESIGN: Prospective, observational cohort study. PARTICIPANTS: Two hundred thirty-six patients with glaucoma followed up for an average of 4.3±1.5 years. METHODS: Vision-related disability was assessed by the 25-item National Eye Institute Visual Function Questionnaire (NEI VFQ-25) at baseline and at the end of follow-up. A latent transition analysis model was used to categorize NEI VFQ-25 results and to estimate the probability of developing vision-related disability during follow-up. Patients were tested with standard automated perimetry (SAP) at 6-month intervals, and evaluation of rates of visual field change was performed using mean sensitivity (MS) of the integrated binocular visual field. Baseline disease severity, rate of visual field loss, and duration of follow-up were investigated as predictive factors for development of disability during follow-up. MAIN OUTCOME MEASURES: The relationship between baseline and rates of visual field deterioration and the probability of vision-related disability developing during follow-up. RESULTS: At baseline, 67 of 236 (28%) glaucoma patients were classified as disabled based on NEI VFQ-25 results, whereas 169 (72%) were classified as nondisabled. Patients classified as nondisabled at baseline had 14.2% probability of disability developing during follow-up. Rates of visual field loss as estimated by integrated binocular MS were almost 4 times faster for those in whom disability developed versus those in whom it did not (-0.78±1.00 dB/year vs. -0.20±0.47 dB/year, respectively; P < 0.001). In the multivariate model, each 1-dB lower baseline binocular MS was associated with 34% higher odds of disability developing over time (odds ratio [OR], 1.34; 95% confidence interval [CI], 1.06-1.70; P = 0.013). In addition, each 0.5-dB/year faster rate of loss of binocular MS during follow-up was associated with a more than 3.5 times increase in the risk of disability developing (OR, 3.58; 95% CI, 1.56-8.23; P = 0.003). CONCLUSIONS: A new methodology for classification and analysis of change in patient-reported quality-of-life outcomes allowed construction of models for predicting vision-related disability in glaucoma.

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.

Glaucoma and Driving Risk under Simulated Fog Conditions.

PURPOSE: We evaluate driving risk under simulated fog conditions in glaucoma and healthy subjects. METHODS: This cross-sectional study included 41 glaucoma patients and 25 age-matched healthy subjects who underwent driving simulation. Tests consisted of curve negotiation without and with fog preview at 30 m of distance and two controlled speeds (slow and fast). Inverse time-to-line crossing (invTLC) was used as metric to quantify risk; higher invTLC values indicating higher risk, as less time is available to avoid drifting out of the road. Piecewise regression models were used to investigate the relationship between differences in invTLC in fog and nonfog conditions and visual field loss. RESULTS: Glaucoma patients had greater increase in driving risk under fog compared to controls, as indicated by invTLC differences (0.490 ± 0.578 s-1 and 0.208 ± 0.106 s-1, respectively; P = 0.002). Mean deviation (MD) of the better eye was significantly associated with driving risk under fog, with a breakpoint of -9 dB identified by piecewise regression. For values below the breakpoint, each 1 dB lower MD of better eye was associated with 0.117 s-1 higher invTLC under fast speed (adjusted R2 = 57.9%; P < 0.001). CONCLUSIONS: Glaucoma patients have a steeper increase in driving risk under fog conditions when compared to healthy subjects, especially when the severity of visual field damage falls below -9 dB of MD in the better eye. TRANSLATIONAL RELEVANCE: By investigating the relationship between driving risk and disease severity breakpoint, this study may provide guidance to clinicians in recognizing glaucoma patients who may be unfit to drive in complex situations such as fog.

Association between Intraocular Pressure and Rates of Retinal Nerve Fiber Layer Loss Measured by Optical Coherence Tomography.

PURPOSE: To evaluate the relationship between intraocular pressure (IOP) and rates of retinal nerve fiber layer (RNFL) thickness change over time measured by spectral-domain (SD) optical coherence tomography (OCT). DESIGN: Observational cohort study. PARTICIPANTS: The study involved 547 eyes of 339 patients followed up for an average of 3.9±0.9 years. Three hundred eight (56.3%) had a diagnosis of glaucoma and 239 (43.7%) were considered glaucoma suspects. METHODS: All eyes underwent imaging using the Spectralis SD OCT (Heidelberg Engineering GmbH, Heidelberg, Germany), along with IOP measurements and standard automated perimetry (SAP). Glaucoma progression was defined as a result of "Likely Progression" from the Guided Progression Analysis software for SAP. Linear mixed models were used to investigate the relationship between average IOP during follow-up and rates of RNFL thickness change, while taking into account potential confounding factors such as age, race, corneal thickness, and baseline disease severity. MAIN OUTCOME MEASURES: The association between IOP and rates of global and sectorial RNFL thickness loss measured by SD OCT. RESULTS: Forty-six eyes (8.4%) showed progression on SAP during follow-up. Rates of global RNFL thickness change in eyes that progressed by SAP were faster than in those that did not progress (-1.02 vs. -0.61 µm/year, respectively; P = 0.002). For progressing eyes, each 1-mmHg higher average in IOP during follow-up was associated with an additional average loss of 0.20 µm/year (95% confidence interval [CI]: 0.08 to 0.31 µm/year; P < 0.001) of global RNFL thickness versus only 0.04 µm/year (95% CI: 0.01 to 0.07 µm/year; P = 0.015) for nonprogressing eyes. The largest associations between IOP and rates of RNFL change were seen for measurements from the temporal superior and temporal inferior sectors, whereas the smallest association was seen for measurements from the nasal sector. CONCLUSIONS: Higher levels of IOP during follow-up were associated with faster rates of RNFL loss over time measured by SD OCT. These findings support the use of SD OCT RNFL thickness measurements as biomarkers for the evaluation of the efficacy of IOP-lowering therapies to slow down the rate of disease progression.

Asymmetric Macular Structural Damage Is Associated With Relative Afferent Pupillary Defects in Patients With Glaucoma.

PURPOSE: We examined the relationship between relative afferent pupillary defects (RAPDs) and macular structural damage measured by macular thickness and macular ganglion cell-inner plexiform layer (mGCIPL) thickness in patients with glaucoma. METHODS: A cross-sectional study was done of 106 glaucoma patients and 85 healthy individuals from the Diagnostic Innovations in Glaucoma Study. All subjects underwent standard automated perimetry (SAP) and optic nerve and macular imaging using Cirrus Spectral Domain Optical Coherence Tomography (SDOCT). Glaucoma was defined as repeatable abnormal SAP or progressive glaucomatous changes on stereo photographs. Pupil responses were assessed using an automated pupillometer, which records the magnitude of RAPD (RAPD score), with additional RAPD scores recorded for each of a series of colored stimuli (blue, red, green, and yellow). The relationship between RAPD score and intereye differences (right minus left eye) in circumpapillary retinal nerve fiber layer (cpRNFL) thickness, mGCIPL, macular thickness, and SAP mean deviation (MD), was examined using linear regression. RESULTS: There was fair correlation between RAPD score and asymmetric macular structural damage measured by intereye difference in mGCIPL thickness (R(2) = 0.285, P < 0.001). The relationship between RAPD score and intereye difference in macular thickness was weaker (R(2) = 0.167, P < 0.001). Intereye difference in cpRNFL thickness (R(2) = 0.350, P < 0.001) and SAP MD (R(2) = 0.594, P < 0.001) had stronger association with RAPD scores compared to intereye difference in mGCIPL and macular thickness. CONCLUSIONS: Objective assessment of pupillary responses using a pupillometer was associated with asymmetric macular structural damage 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 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.

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.

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.

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.

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.

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.