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.

Event-based analysis of visual field change can miss fast glaucoma progression detected by a combined structure and function index.

PURPOSE: To investigate the relationship between progression assessed by the visual field guided progression analysis (GPA) and rates of structural and functional change in glaucoma eyes. METHODS: This was a longitudinal observational study of 135 eyes of 97 patients with glaucoma followed for an average of 3.5 ± 0.9 years. All patients had standard automated perimetry (SAP) and retinal nerve fiber layer (RNFL) analysis with spectral domain optical coherence tomography (SDOCT), with an average of 6.8 ± 2.3 visits. A control group of healthy eyes followed longitudinally was used to estimate age-related change. Visual field progression was assessed using the Humphrey Field Analyzer GPA. Estimates of retinal ganglion cell counts from SAP and SDOCT were used to obtain a combined index of glaucomatous damage (RGC index) according to a previously described algorithm. Progression by SDOCT and the retinal ganglion cell (RGC) index were defined as statistically significant (P < 0.05) slopes of change that were also faster than age-related change estimated from healthy eyes. RESULTS: From the 135 eyes, 15 (11%) progressed by GPA, 21 (16%) progressed by SDOCT, and 31 (23%) progressed by the RGC index. Twenty-one eyes showed progression by the RGC index that was missed by the GPA. These eyes had an average rate of change in estimated RGC counts of - 28,910 cells/year, ranging from two to nine times faster than expected age-related losses. CONCLUSION: Many glaucomatous eyes that are not found to be progressing by GPA may actually have fast rates of change as detected by a combined index of structure and function.

Frequency of Testing to Detect Visual Field Progression Derived Using a Longitudinal Cohort of Glaucoma Patients.

PURPOSE: To determine the time required to detect statistically significant progression for different rates of visual field loss using standard automated perimetry (SAP) when considering different frequencies of testing using a follow-up scheme that resembles clinical practice. DESIGN: Observational cohort study. PARTICIPANTS: One thousand seventy-two eyes of 665 patients with glaucoma followed up over an average of 4.3±0.9 years. METHODS: Participants with 5 or more visual field tests over a 2- to 5-year period were included to derive the longitudinal measurement variability of SAP mean deviation (MD) using linear regressions. Estimates of variability then were used to reconstruct real-world visual field data by computer simulation to evaluate the time required to detect progression for various rates of visual field loss and different frequencies of testing. The evaluation was performed using a follow-up scheme that resembled clinical practice by requiring a set of 2 baseline tests and a confirmatory test to identify progression. MAIN OUTCOME MEASURES: Time (in years) required to detect progression. RESULTS: The time required to detect a statistically significant negative MD slope decreased as the frequency of testing increased, albeit not proportionally. For example, 80% of eyes with an MD loss of -2 dB/year would be detected after 3.3, 2.4, and 2.1 years when testing is performed once, twice, and thrice per year, respectively. For eyes with an MD loss of -0.5 dB/year, progression can be detected with 80% power after 7.3, 5.7, and 5.0 years, respectively. CONCLUSIONS: This study provides information on the time required to detect progression using MD trend analysis in glaucoma eyes when different testing frequencies are used. The smaller gains in the time to detect progression when testing is increased from twice to thrice per year suggests that obtaining 2 reliable tests at baseline followed by semiannual testing and confirmation of progression through repeat testing in the initial years of follow-up may provide a good compromise for detecting progression, while minimizing the burden on health care resources in clinical practice.

Hazard Detection During Simulated Driving in Glaucoma Patients.

PRCIS: In this cross-sectional study, glaucoma patients showed slower reaction times (RTs) to hazardous situations when compared with control subjects during simulated driving. Worse RTs were associated with a greater magnitude of visual field loss. PURPOSE: The purpose of this study was to evaluate the impact of different hazardous traffic conditions on driving performance in glaucoma patients using a high-fidelity driving simulator. METHODS: The cross-sectional study was performed with 52 glaucoma patients and 15 control subjects. A series of hazard scenarios were presented, such as pedestrians crossing the street unexpectedly or vehicles suddenly pulling into the driver's lane. RTs in seconds (s) from first the evidence of a hazard to the time it took the driver to take the foot off the gas pedal ("Gas Off") and the time it took to depress the brake pedal ("Brake On") were compared between groups. RESULTS: Overall, mean RTs were statistically significantly slower in glaucoma patients (3.39±3.88 s) compared with controls (2.39±1.99 s; P =0.005) for the "Brake On" task but not for the "Gas Off" task (2.74±3.42 vs. 2.13±1.91 s, respectively; P =0.120). For subjects with glaucoma, multivariable models adjusted for age, gender, race, and visual acuity demonstrated significantly slower RTs for worse values of binocular mean sensitivity for both "Gas Off" and "Brake On" tasks (1.12 and 1.14 s slower per 10 dB worse; P =0.009 and P <0.001, respectively). Subjects with glaucoma took significantly longer times to brake for smaller (low saliency) hazards compared with larger (high saliency) hazards ( P =0.027). CONCLUSIONS: RTs in response to hazardous driving situations were slower for glaucoma patients compared with controls. Individualized assessment of driving fitness using hazardous scenarios in driving simulators could be helpful in providing an assessment of driving risk in glaucoma patients.

Gonioscopy-Assisted Transluminal Trabeculotomy for Glaucoma: 1-Year Outcomes and Success Predictors.

PRCIS: Our results suggest gonioscopy-assisted transluminal trabeculotomy (GATT) as an effective and safe option for the surgical management of open-angle glaucoma (OAG). Older age was the only risk factor for failure in our analysis. PURPOSE: To report 12-month clinical outcomes, safety profile and success predictors of GATT in patients with OAG. PATIENTS AND METHODS: A retrospective study of patients (18 y old and above) with medically uncontrolled OAG who underwent GATT as a solo procedure or combined with phacoemulsification (PHACO-GATT) between January 2018 and January 2020. Success at 12 months (primary outcome) was defined as intraocular pressure (IOP) <15 mm Hg, with an IOP reduction of at least 20%, OR a reduction of at least 2 glaucoma medications, compared with baseline. Secondary outcomes were success predictors and safety parameters. RESULTS: A total of 73 eyes (GATT=38; PHACO-GATT=35) from 58 patients with a mean age of 54.8±11.6 years were included. Overall, after 12 months of follow-up, the mean IOP was reduced from 24.9±8.5 to 12.1±2.1 mm Hg (P<0.001). The mean number of glaucoma medications was reduced from 3.5±0.7 to 1.2±1.2 (P<0.001). The success rate was 87% at 12 months, with no significant differences between GATT (85%) and PHACO-GATT (91%) eyes (P=0.330). Age was the only factor significantly associated with surgical success (hazard ratio=1.35; P=0.012; after adjusting for preoperative IOP and number of glaucoma medications). Patients older than 60 years had a significant greater chance of failure (hazard ratio=10.96; P=0.026) compared with those younger than 60 years. The most common postoperative complication was transient hyphema (39%; median duration, 5 d). No sight-threatening adverse event was documented. CONCLUSIONS: GATT was effective and safe at lowering IOP with or without cataract extraction in OAG. Patients 60 years or older had a higher risk of failure compared with those younger in age.

Gonioscopy-assisted transluminal trabeculotomy (GATT) outcomes in eyes with open-angle glaucoma resistant to maximum treatment.

PURPOSE: To report the initial 2 years' learning curve on gonioscopy-assisted transluminal trabeculotomy performed using the thermally blunted suture technique and review the factors that could potentially affect the outcome. METHODS: This retrospective study evaluated 100 eyes from 89 participants with glaucoma resistant to maximum clinical treatment, which was defined as having an intraocular pressure >21 mmHg in addition to three or four different hypotensive drugs. Intraocular pressure values at baseline, 1 week, and at 1, 2, 3, 6, 12, and 24 months of follow-up and details regarding the need of antiglaucoma medication and further glaucoma surgery were recorded. Eyes that required further surgical intervention for intraocular pressure control were considered as failure. RESULTS: A total of 51 eyes were subjected to isolated gonioscopy-assisted transluminal trabeculotomy, and 49 eyes were subjected to gonioscopy-assisted transluminal trabeculotomy + cataract extraction at the same surgical time. A statistically significant difference was observed between overall mean follow-up intraocular pressure and mean preoperative intraocular pressure (p<0.001) in all follow-up visits. When the extent of treatment was evaluated, patients with an extension of 360° did not exhibit statistically significantly lower mean intraocular pressure than those with other extensions. Hyphema was the only complication presented in 50 eyes (50%), but all had spontaneous resolution within 4 weeks. A total of 26 eyes (26%) required additional conventional trabeculectomy due to uncontrolled intraocular pressure, especially those who previously underwent vitreoretinal surgery. CONCLUSIONS: Gonioscopy-assisted transluminal trabeculotomy, besides being an apparently safe procedure, results in satisfactory success rates even during the surgeon's initial learning curve. The technique was effective in decreasing intraocular pressure and medication burden.

Comparing the Rule of 5 to Trend-based Analysis for Detecting Glaucoma Progression on OCT.

PURPOSE: The rule of 5 is a simple rule for detecting retinal nerve fiber layer (RNFL) change on spectral-domain OCT (SD-OCT), in which a loss of 5 µm of global RNFL on a follow-up test is considered evidence of significant change when compared with the baseline. The rule is based on short-term test-retest variability of SD-OCT and is often used in clinical practice. The purpose of this study was to compare the rule of 5 with trend-based analysis of global RNFL thickness over time for detecting glaucomatous progression. DESIGN: Prospective cohort. PARTICIPANTS: A total of 300 eyes of 210 glaucoma subjects followed for an average of 5.4±1.5 years with a median of 11 (interquartile range, 7-14) visits. METHODS: Trend-based analysis was performed by ordinary least-squares (OLS) linear regression of global RNFL thickness over time. For estimation of specificity, false-positives were obtained by assessing for progression on series of randomly permutated follow-up visits for each eye, which removes any systematic trend over time. The specificity of trend-based analysis was matched to that of the rule of 5 to allow meaningful comparison of the "hit rate," or the proportion of glaucoma eyes categorized as progressing at each time point, using the original sequence of visits. MAIN OUTCOME MEASURES: Comparison between hit rates of trend-analysis versus rule of 5 at matched specificity. RESULTS: After 5 years, the simple rule of 5 identified 37.5% of eyes as progressing at a specificity of 81.1%. At the same specificity, the hit rate for trend-based analysis was significantly greater than that of the rule of 5 (62.9% vs. 37.5%; P < 0.001). If the rule of 5 was required to be repeatable on a consecutive test, specificity improved to 93.4%, but hit rate decreased to 21.0%. At this higher specificity, trend-based analysis still had a significantly greater hit rate than the rule of 5 (47.4% vs. 21.0%, respectively; P < 0.001). CONCLUSIONS: Trend-based analysis was superior to the simple rule of 5 for identifying progression in glaucoma eyes and should be preferred as a method for longitudinal assessment of global SD-OCT RNFL change over time.

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.

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.

Visual Crowding in Glaucoma.

Purpose: Crowding refers to the phenomenon in which objects that can be recognized when viewed in isolation are unrecognizable in clutter. Crowding sets a fundamental limit to the capabilities of the peripheral vision and is essential in explaining performance in a broad array of daily tasks. Due to the effects of glaucoma on peripheral vision, we hypothesized that neural loss in the disease would lead to stronger effects of visual crowding. Methods: Subjects were asked to discriminate the orientation of a target letter when presented with surrounding flankers. The critical spacing value (scritical), which was required for correct discrimination of letter orientation, was obtained for each quadrant of the visual field. scritical values were correlated with standard automated perimetry (SAP) mean sensitivity (MS) and optical coherence tomography (OCT) retinal nerve fiber layer (RNFL) thickness measurements. Results: The study involved 13 subjects with mild glaucomatous visual field loss and 13 healthy controls. Glaucomatous eyes had significantly greater (worse) scritical than controls (170.4 ± 27.1 vs. 145.8 ± 28.0 minimum of visual angle, respectively; P = 0.007). scritical measurements were significantly associated with RNFL thickness measurements (R2 = 26%; P < 0.001) but not with SAP MS (P = 0.947). Conclusions: In glaucoma patients, a pronounced visual crowding effect is observed, even in the presence of mild visual field loss on standard perimetry. scritical was associated with the amount of neural loss quantified by OCT. These results may have implications for understanding how glaucoma patients are affected in daily tasks where crowding effects may be significant.

Mobile Telephone Use and Reaction Time in Drivers With Glaucoma.

Importance: Combining mobile telephone use with driving is not unusual. However, distracted driving limits driving performance because of limited capacity for persons to divide attention. Objectives: To investigate the frequency of mobile telephone use while driving and to assess whether patients with glaucoma had a disproportionate decrease in driving performance while conversing on a mobile telephone compared with healthy participants. Design, Setting, and Participants: Cross-sectional study of surveys collected from 112 patients with glaucoma and 70 control participants investigating mobile telephone use while driving. A randomly selected subgroup of 37 patients with glaucoma and 28 controls drove in a driving simulator to investigate peripheral event detection performance during distracted driving at the Visual Performance Laboratory, Duke University, Durham, North Carolina. Data collection was performed from December 1, 2016, through April 30, 2017. Exposures: Participants answered a survey and submitted to a driving simulation test with and without mobile telephone use. Main Outcomes and Measures: Survey answers were collected, and distracted driving performance, assessed by reaction time to peripheral stimuli, was analyzed. Results: Of the 182 participants who answered the survey, the 112 participants with glaucoma included 56 women (50.0%) and had a mean (SD) age of 73.6 (9.6) years. The 70 controls included 49 women (70.0%) and had a mean (SD) age of 68.4 (10.9) years. When asked about mobile telephone use while driving, 30 patients with glaucoma (26.8%) admitted rarely using and 2 (1.8%) sometimes using it. In the control group, 20 participants (28.6%) admitted rarely using and 2 (2.9%) sometimes using the telephone while driving (P = .80). Reaction times to peripheral stimuli were significantly longer among patients with glaucoma compared with controls during mobile telephone use (median [interquartile range], 1.86 [1.42-2.29] seconds vs 1.14 [0.98-1.59] seconds; P = .02). Compared with driving performance while not using a mobile telephone, the mean (SD) increase of 0.85 (0.60) second in reaction time while conversing on the mobile telephone among patients with glaucoma was significantly greater than the mean (SD) increase of 0.68 (0.83) second for controls (P = .03). Conclusions and Relevance: This study's findings indicate that patients with glaucoma use mobile telephones while driving as frequently as healthy participants. However, the findings also suggest that patients with glaucoma may experience a greater decline than healthy participants in their ability to detect peripheral events while driving when also talking on a mobile telephone. Patients with glaucoma should be informed that they may have a higher driving risk that may be worsened by distractions, such as mobile telephone use.

Macular Pigment and Visual Function in Patients With Glaucoma: The San Diego Macular Pigment Study.

Purpose: Although recent studies have shown that macular pigment (MP) is significantly lower in glaucoma patients, this relationship merits further investigation. Methods: This cross-sectional study included 85 glaucoma patients and 22 controls. All subjects had standard automated perimetry (SAP) and retinal nerve fiber layer (RNFL) thickness measurements. Intake of lutein (L) and zeaxanthin (Z) was estimated using a novel dietary screener. The Heidelberg Spectralis dual-wavelength autofluorescence (AF) technology was employed to study the relationship between MP and glaucoma. The association between MP volume and glaucoma was investigated using linear regression models accounting for potential confounding factors. Results: Glaucoma patients had significantly worse SAP mean deviation (MD) and lower RNFL thickness in the study eye compared to control subjects (P < 0.001 for both). MP (volume) was comparable between groups (P = 0.436). In the univariable model, diagnosis of glaucoma was not associated with MP volume (R2 = 1.22%; P = 0.257). Dietary intake of L and Z was positively and significantly related to MP in the univariable (P = 0.022) and multivariable (P = 0.020) models. Conclusions: These results challenge previous studies that reported that glaucoma is associated with low MP. Dietary habits were found to be the main predictor of MP in this sample. Further research is merited to better understand the relationship between glaucoma, MP, and visual performance in these patients.

A Prospective Longitudinal Study to Investigate Corneal Hysteresis as a Risk Factor for Predicting Development of Glaucoma.

PURPOSE: To investigate the role of corneal hysteresis (CH) as a risk factor for development of glaucoma. DESIGN: Prospective observational cohort study. METHODS: Two hundred and eighty-seven eyes of 199 patients suspected of having glaucoma were followed for an average of 3.9 ± 1.8 years. All eyes had normal visual fields at baseline. Development of glaucoma was defined as occurrence of 3 consecutive abnormal standard automated perimetry tests during follow-up, defined as pattern standard deviation (PSD) < 5%, and/or Glaucoma Hemifield Test outside normal limits. Measurements of CH were acquired at baseline using the Ocular Response Analyzer (ORA). Univariable and multivariable Cox regression models were used to investigate baseline factors associated with development of visual field loss over time. RESULTS: Fifty-four (19%) eyes developed repeatable visual field defects during follow-up. Measurements of CH at baseline were significantly lower in patients who developed glaucoma vs those who did not (9.5 ± 1.5 mm Hg vs 10.2 ± 2.0 mm Hg; P = .012). Each 1-mm Hg lower CH was associated with an increase of 21% in the risk of developing glaucoma during follow-up (95% confidence interval [CI]: 1.04-1.41; P = .013). In a multivariable model adjusting for age, intraocular pressure, central corneal thickness, PSD, and treatment, CH was still predictive of development of glaucoma (hazard ratio = 1.20; 95% CI: 1.01-1.42; P = .040). CONCLUSION: Baseline lower CH measurements were significantly associated with increased risk of developing glaucomatous visual field defects over time. The prospective longitudinal design of this study supports a role of CH as a risk factor for developing glaucoma.

Optical Coherence Tomography Angiography Macular Vascular Density Measurements and the Central 10-2 Visual Field in Glaucoma.

PURPOSE: To evaluate the association between macula vascular density assessed by optical coherence tomography angiography (OCT-A) and central visual field (VF) threshold sensitivities in healthy, glaucoma suspect, and glaucoma patients. METHODS: A total of 185 eyes from 38 healthy participants, 31 glaucoma suspects, 72 mild glaucoma patients, and 44 moderate/severe glaucoma patients from the Diagnostic Innovations in Glaucoma Study who underwent OCT-A images of the macula and 10-2 VF testing were enrolled in this observational cross-sectional study. The relationship between central VF mean sensitivity (MS) and superficial macula whole-image vessel density (wiVD), and the relationship between the MS of the 4 central points of the 10-2 VF (MS4) and parafoveal vessel density (pfVD), were assessed using linear regression models. RESULTS: Mean wiVD (52.5%, 49.8%, 49.4% and 45.2%, respectively) and mean pfVD (54.9%, 52.1%, 51.8% and 47.7%, respectively) were found to be significantly higher in healthy eyes and glaucoma suspect eyes compared with glaucoma eyes with mild and moderate/severe disease [analysis of covariance (ANCOVA) P<0.001]. The univariate associations between 10-2 MS and wiVD (R=26.9%) and between 10-2 MS4 and pfVD (R=16.8%) were statistically significant (P<0.001 for both). After adjusting for scan quality, age, sex and intraocular pressure, superficial macula wiVD and pfVD were still independently associated with central VF loss. Macula wiVD performed better [area under the receiver operator characteristic (AUROC)=0.70] than ganglion cell complex thickness (AUROC=0.50) for differentiating between glaucoma suspect and healthy eyes (P=0.010). CONCLUSIONS: Loss of OCT-A macula vessel density is associated with central 10-2 VF defects. Macula vessel density is a clinically relevant parameter that may enhance monitoring of glaucoma suspects and patients.

The Association Between Macula and ONH Optical Coherence Tomography Angiography (OCT-A) Vessel Densities in Glaucoma, Glaucoma Suspect, and Healthy Eyes.

PURPOSE: To evaluate strength of associations between optical coherence tomography (OCT)-angiography vessel density (VD) measurements in the macula and peripapillary region of the optic nerve head (ONH) with standard structural OCT thickness measures. MATERIALS AND METHODS: This cross-sectional study included 333 eyes of 219 primary open-angle glaucoma patients, 41 glaucoma suspects, and 73 healthy participants from the Diagnostic Innovations in Glaucoma Study (DIGS) with good quality OCT angiography images. The strength of associations between microvasculature measures in the ONH retinal nerve fiber layer (RNFL) and superficial macula layer was assessed using linear regression models. Associations between ONH and macula VD, and circumpapillary (cp) RNFL thickness and macular ganglion cell complex (mGCC) measures were also evaluated. RESULTS: The strength (r) of associations among VD and thickness measures of ONH and macula ranged from 14.1% to 69.4%; all were statistically significant (P<0.001). The association between ONH and macula whole-image VD (r=41.0%) was significantly weaker than the relationship between mGCC and cpRNFL thickness (r=69.4%, P<0.001). Although both cpRNFL and mGCC thicknesses tended to be more strongly associated with ONH VD (r=39.2% and 26.7%, respectively) than macula VD (r=27.5% and 17.7%, respectively), differences did not reach statistical significance (P=0.050 and P=0.113, respectively). CONCLUSIONS: The strength of the association of VD with cpRNFL and mGCC thicknesses varies by retinal layer. The weaker association of macula VD compared with ONH VD with tissue thickness may be due to differences in micorovasculature between the macula and ONH.

Optical coherence tomography analysis of hydrofluoric acid decontamination of human cornea by mannitol solution.

PURPOSE: To evaluate the efficacy of mannitol solution as a decontamination agent on the chemical burn of the human corneas. METHODS: Eight donor corneas from an eye bank were exposed to 25µl of 2.5% hydrofluoric acid (HF) solution on a filter paper for 20s. Three eyes were rinsed with 1000ml of mannitol 20% for 15min immediately after removal of the filter paper, 3 other were rinsed with sodium chloride (NaCl) 0.9% (1000ml for 15min) and two eyes were not rinsed. Microstructural changes were monitored in the time domain by optical coherence tomography (OCT) imaging for 75min. RESULTS: NaCl reduced the penetration depth to approximately half the thickness of the cornea at 15min; scattering within the anterior cornea was higher than that for the unrinsed eye. With mannitol, no increased scattering was observed in the posterior part of the corneal stroma within a time period of 1h after rinsing. OCT images revealed low-scattering intensity within the anterior stroma at the end of the rinsing period. CONCLUSION: In eye bank human corneas, mannitol proved to be an efficient agent to decontaminate HF burn.

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.

Impact of Normal Aging and Progression Definitions on the Specificity of Detecting Retinal Nerve Fiber Layer Thinning.

PURPOSE: To evaluate the specificity of current definitions used to identify progressive change of the average peripapillary retinal nerve fiber layer (RNFL) thickness measurements obtained on optical coherence tomography (OCT) imaging. DESIGN: Prospective observational cohort study. METHODS: Setting: University of California, San Diego. STUDY POPULATION: Seventy-five eyes from 45 normal participants. OBSERVATION PROCEDURE: Patients were seen at an average of 5.7 visits over 3.2 years, to determine the age-related average RNFL thickness changes and longitudinal measurement variability. Slope and variability estimates were used to reconstruct "real-world" OCT imaging measurements with computer simulations. MAIN OUTCOME MEASURE: False-positive rates for progression in normal eyes using different definitions. RESULTS: The estimated normal average RNFL thickness change over time was -0.54 ± 0.23 µm/year (P < .001). Even with a recent definition of progression that appeared to guarantee a high level of specificity by accounting for normal aging (requiring a significant negative slope that was more negative than the 5% lower limit of aging), 18% simulated normal eyes were still falsely identified as having progressed after 5 years of annual testing in a clinical practice scenario. However, this was reduced to 8% and 4% when trend-based analysis of progression was performed after adjustments using the mean and 5% lower limit of normal rates of aging, respectively. CONCLUSIONS: This study highlights how current definitions for detecting RNFL thinning have an unacceptably poor level of specificity, and that more stringent definitions are required to avoid misleading interpretations of progression on OCT imaging in clinical practice.

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.

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.