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To investigate the association between corneal hysteresis (CH) and rates of optic nerve head whole image capillary density (wiCD) loss over time in open-angle glaucoma (OAG).Observational cohort.One hundred seventy-four eyes (122 OAG and 52 glaucoma suspect eyes) from 112 patients over more than 2 years and 4 visits or more.Baseline CH measurements were acquired with the Ocular Response Analyzer. Linear mixed-effect models were designed to investigate the effect of CH, average intraocular pressure (IOP) during follow-up, and baseline visual field (VF) mean deviation (MD) on the rates of wiCD loss and circumpapillary retinal nerve fiber layer (cpRNFL) thinning over time, while adjusting for confounders. Interaction between CH or baseline MD and average IOP during follow-up were included in final models to evaluate the effect of baseline MD or average IOP during follow-up on structural changes for different values of CH.Effect of CH, IOP, and baseline MD on the rates of wiCD loss and cpRNFL thinning over time.The average follow-up time was 3.9 years. In the multivariable model, non-Black race, higher average IOP during follow-up, lower baseline CH, lower baseline VF MD, and higher numbers of IOP-lowering medications were associated with faster rates of wiCD loss over time. For CH values 6 mmHg and 12 mmHg, every 1-mmHg increase in average IOP during follow-up was associated with 0.23% per year faster and 0.07% per year slower rates of wiCD loss over time, respectively. While every 1-mmHg decrease in CH was associated with 1.89% per year faster rate of wiCD loss for MD of -12 dB, it was associated with 0.81% per year faster rate of wiCD loss for MD of -3 dB.Lower CH values were significantly associated with faster rates of wiCD loss over time. In eyes with lower CH, both higher average IOP during follow-up and more severe glaucoma damage at baseline were associated with faster rates of wiCD loss and cpRNFL thinning. These results support CH as a useful parameter for risk assessment of glaucoma progression.

To use longitudinal optical coherence tomography (OCT) and OCT angiography (OCTA) data to detect glaucomatous visual field (VF) progression with a supervised machine learning approach.Prospective cohort study.One hundred ten eyes of patients with suspected glaucoma (33.6%) and patients with glaucoma (66.4%) with a minimum of 5 24-2 VF tests and 3 optic nerve head and macula images over an average follow-up duration of 4.1 years were included. VF progression was defined using a composite measure including either a "likely progression event" on Guided Progression Analysis, a statistically significant negative slope of VF mean deviation or VF index, or a positive pointwise linear regression event. Feature-based gradient boosting classifiers were developed using different subsets of baseline and longitudinal OCT and OCTA summary parameters. The area under the receiver operating characteristic curve (AUROC) was used to compare the classification performance of different models.VF progression was detected in 28 eyes (25.5%). The model with combined baseline and longitudinal OCT and OCTA parameters at the global and hemifield levels had the best classification accuracy to detect VF progression (AUROC = 0.89). Models including combined OCT and OCTA parameters had higher classification accuracy compared with those with individual subsets of OCT or OCTA features alone. Including hemifield measurements significantly improved the models' classification accuracy compared with using global measurements alone. Including longitudinal rates of change of OCT and OCTA parameters (AUROCs = 0.80-0.89) considerably increased the classification accuracy of the models with baseline measurements alone (AUROCs = 0.60-0.63).Longitudinal OCTA measurements complement OCT-derived structural metrics for the evaluation of functional VF loss in patients with glaucoma.

To determine how the frequency of testing affects the time required to detect statistically significant glaucoma progression for circumpapillary retinal nerve fiber layer (cpRNFL) with optical coherence tomography (OCT) and circumpapillary capillary density (cpCD) with OCT angiography (OCTA).Retrospective, observational cohort study.In this longitudinal study, 156 eyes of 98 patients with glaucoma followed up over an average of 3.5 years were enrolled. Participants with 4 or more OCT and OCTA tests were included to measure the longitudinal rates of cpRNFL thickness and cpCD change over time using linear regression. Estimates of variability were then used to re-create real-world cpRNFL and cpCD data by computer simulation to evaluate the time required to detect progression for various loss rates and different testing frequencies.The time required to detect a statistically significant negative cpRNFL and cpCD slope decreased as the testing frequency increased, albeit not proportionally. cpCD detected progression slightly earlier than cpRNFL. Eighty percent of eyes with a cpCD loss of -1%/y were detected after 6.0, 4.2, and 4 years when testing was performed 1, 2, and 3 times per year, respectively. Progression in 80% of eyes with a cpRNFL loss of -1 µm/y was detected after 6.3, 5.0, and 4.2 years, respectively.cpRNFL and cpCD are comparable in detecting progression. As there were only small changes in the time to detect progression when testing increased from 2 to 3 times per year, testing twice per year may provide sufficient information for detecting progression with either OCT or OCTA in clinical settings.

To investigate the relationship of longitudinal changes in macular vessel density (VD) from OCT angiography and in ganglion cell complex (GCC) from OCT with central visual field (VF) in eyes with early glaucoma.Observational cohort.A total of 95 eyes, 37 preperimetric and 58 with early glaucoma (24-2 VF mean deviation [MD] ≥ -6 decibels), with an average follow-up of 3.8 years and 5.3 visits, were included.Whole-image VD (wiVD) and whole-image GCC (wiGCC) and parafoveal scans, as well as localized regions of interest (LROIs), hemiretinae of whole images, and superior, inferior, temporal, and nasal sectors of parafoveal maps, were matched with central VF locations. Age-adjusted rates of change of VD, GCC, mean sensitivity of VF locations, and 10-2 VF MD were calculated using linear mixed-effect models. Normalized rates of change were calculated for comparison of change rates in wiVD and wiGCC.Structure-function (SF) correlations of VD and GCC with central VF measurement change rates and comparison of different correlations of SF relationships after bootstrapping the difference of the correlation coefficients.Vessel density loss and GCC thinning demonstrated significant correlations with central VF damage, globally and with most LROIs. The SF correlation (r, 95% confidence interval [CI]) between wiVD and 10-2 VF MD change rates was 0.42 [0.24, 0.58], whereas it was 0.27 [0.08, 0.45] between wiGCC and 10-2 VF MD changes rates (all P0.05). In contrast to GCC thinning, VD loss in the parafoveal sectors demonstrated significant correlations with central VF damage in inferior and temporal sectors. Differences in the relationship of SF with central VF damage were not significant between VD loss and GCC thinning. The mean (95% CI) normalized change rates of wiVD (-7.40 [-7.71 to 7.09] %/year) was faster than that of wiGCC (-2.39 [-2.94 to 1.84] %/year) (P0.05).Rates of VD loss and GCC thinning are associated with central VF loss over time. Assessment of both macular VD and GCC thickness should be considered for evaluation of glaucoma progression.

To evaluate the effects of pressure changes induced by a multipressure dial (MPD) on circumpapillary retinal nerve fiber layer (RNFL) and capillary density (CD) measurements in patients with glaucoma using OCT angiography (OCTA).Prospective interventional study.Twenty-four patients with primary open-angle glaucoma.One eye of each patient underwent negative pressure application with the MPD. The MPD alters intraocular pressure (IOP) relative to atmospheric pressure by generating a negative pressure vacuum within a goggle chamber that is placed over the eye. Each participant underwent serial high density OCTA imaging (AngioVue) of the optic nerve head at different negative pressure increments of -5 mmHg, starting from 0 mmHg, ending at -20 mmHg, and then returning to baseline. Images were acquired after 2 minutes of sustained negative pressure at each target pressure to allow for stabilization of the retinal structures and microvasculature. The RNFL thickness and CD measurements were automatically calculated using the native AngioVue software, and then exported for analysis.The influence of different levels of negative pressure on circumpapillary RNFL thickness and CD measurements, assessed by a linear mixed-effects model with repeated measures.The mean (± SD) age was 71.0 years (± 7.8 years), the baseline IOP was 17.5 mmHg (± 3.6 mmHg), and there was a mean 24-2 mean deviation of -2.80 dB (± 2.55 dB). Serial circumpapillary CD measurements showed a statistically significant dose-dependent increase from baseline, without negative pressure application, to the maximum negative pressure application of -20 mmHg (difference, 2.27%; P = 0.010). Capillary density measurements then decreased symmetrically when lowering the negative pressure to baseline. Circumpapillary CD measurements at target negative pressures of -10 mmHg, -15 mmHg, and -20 mmHg were significantly higher than the baseline measurements (all P values0.05). Circumpapillary RNFL thickness remained the same throughout different levels of negative pressure.Circumpapillary CD measurements showed a dose-dependent increase with the induction of negative pressure, while RNFL thickness measurements remained unchanged.

PurposeTo evaluate the role of corneal hysteresis (CH) as a risk factor of central visual field (VF) progression in a cohort of glaucoma suspect and glaucoma patients.DesignProspective cohort study.MethodsTwo hundred forty-eight eyes of 143 subjects who were followed for an average of 4.8 years with a minimum of 5 visits with 10-2 and 24-2 VF tests were included. Univariable and multivariable linear mixed-effects models were used to identify characteristics associated with the rate of change over time in 10-2 and 24-2 mean deviation (MD). Mixed-effects logistic regression was used to evaluate characteristics associated with an increased likelihood of event-based 10-2 VF progression based on the clustered pointwise linear regression criterion.ResultsCH was significantly associated with 10-2 and 24-2 VF progression in the univariable trend-based analysis. In multivariable trend-based analyses, lower CH was associated with a faster rate of decline in 10-2 MD (0.07 dB/y per 1 mm Hg, P < .001) but not with 24-2 MD (P=.490). In multivariable event-based analysis, lower CH was associated with an increased likelihood of 10-2 VF progression (odds ratio=1.35 per 1 mm Hg lower, P=.025). Similar results were found in eyes with early glaucomatous damage at the baseline (baseline: 24-2 MD ≥ -6 dB).ConclusionsLower CH was associated with a statistically significant, but relatively small, increased risk of central VF progression on the 10-2 test grid. Given the substantial influence of central VF impairment on the quality of life, clinicians should consider using CH to assess the risk of progression in patients with primary open-angle glaucoma including those with early disease.

PurposeTo compare measurements of global and regional circumpapillary capillary density (cpCD) with retinal nerve fiber layer (RNFL) thickness and characterize their relationship with visual function in early primary open-angle glaucoma (POAG).DesignCross-sectional study.ParticipantsEighty healthy eyes, 64 preperimetric eyes, and 184 mild POAG eyes from the Diagnostic Innovations in Glaucoma Study.MethodsGlobal and regional RNFL thickness and cpCD measurements were obtained using OCT and OCT angiography (OCTA). For direct comparison at the individual and diagnostic group level, RNFL thickness and capillary density values were converted to a normalized relative loss scale.Main outcome measuresRetinal nerve fiber layer thickness and cpCD normalized loss at the individual level and diagnostic group. Global and regional areas under the receiver operating characteristic curve (AUROC) for RNFL thickness and cpCD to detect preperimetric glaucoma and glaucoma, R2 for the strength of associations between RNFL thickness function and capillary density function in diagnostic groups.ResultsBoth global and regional RNFL thickness and cpCD decreased progressively with increasing glaucoma severity (P < 0.05, except for temporal RNFL thickness). Global and regional cpCD relative loss values were higher than those of RNFL thickness (P < 0.05) in preperimetric glaucoma (except for the superonasal region) and glaucoma (except for the inferonasal and superonasal regions) eyes. Race, intraocular pressure (IOP), and cpCD were associated with greater cpCD than RNFL thickness loss in early glaucoma at the individual level (P < 0.05). Global measurements of capillary density (whole image capillary density and cpCD) had higher diagnostic accuracies than RNFL thickness in detecting preperimetric glaucoma and glaucoma (P < 0.05; except for cpCD/RNFL thickness comparison in glaucoma [P= 0.059]). Visual function was significantly associated with RNFL thickness and cpCD globally and in all regions (P < 0.05, except for temporal RNFL thickness-function association [P= 0.070]).ConclusionsAssociations between capillary density and visual function were found in the regions known to be at highest risk for damage in preperimetric glaucoma eyes and all regions of mild glaucoma eyes. In early glaucoma, capillary density loss was more pronounced than RNFL thickness loss. Individual characteristics influence the relative magnitudes of capillary density loss compared with RNFL thickness loss. Retinal nerve fiber layer thickness and microvascular assessments are complementary and yield valuable information for the detection of early damages seen in POAG.

PurposeTo compare convolutional neural network (CNN) analysis of en face vessel density images to gradient boosting classifier (GBC) analysis of instrument-provided, feature-based optical coherence tomography angiography (OCTA) vessel density measurements and OCT retinal nerve fiber layer (RNFL) thickness measurements for classifying healthy and glaucomatous eyes.DesignComparison of diagnostic approaches.MethodsA total of 130 eyes of 80 healthy individuals and 275 eyes of 185 glaucoma patients with optic nerve head (ONH) OCTA and OCT imaging were included. Classification performance of a VGG16 CNN trained and tested on entire en face 4.5×4.5-mm radial peripapillary capillary OCTA ONH images was compared to the performance of separate GBC models trained and tested on standard OCTA and OCT measurements. Five-fold cross-validation was used to test predictions for CNNs and GBCs. Areas under the precision recall curves (AUPRC) were calculated to control for training/test set size imbalance and were compared.ResultsAdjusted AUPRCs for GBC models were 0.89 (95% CI=0.82, 0.92) for whole image vessel density GBC, 0.89 (0.83, 0.92) for whole image capillary density GBC, 0.91 (0.88, 0.93) for combined whole image vessel and whole image capillary density GBC, and 0.93 (0.91, 095) for RNFL thickness GBC. The adjusted AUPRC using CNN analysis of en face vessel density images was 0.97 (0.95, 0.99) resulting in significantly improved classification compared to GBC OCTA-based results and GBC OCT-based results (P ≤ 0.01 for all comparisons).ConclusionDeep learning en face image analysis improves on feature-based GBC models for classifying healthy and glaucoma eyes.

PURPOSE: To characterize the change of ganglion cell complex (GCC) thickness and macula vessel density in eyes diagnosed as being glaucoma suspect eyes with ocular hypertension (OHT) or glaucomatous optic neuropathy (GON). DESIGN: Prospective, longitudinal study. PARTICIPANTS: 83 eyes (24 healthy eyes, 30 OHT eyes, and 29 GON eyes) of 65 subjects who had at least 3 visits were included from the Diagnostic Innovations in Glaucoma Study. The mean follow-up was at least 3 years. METHODS: Optical coherence tomography angiography (OCTA)-based vessel density and OCT-based structural thickness of the 3×3 mm(2) GCC scan slab were evaluated at each visit. The rates of vessel density and thickness change were compared across diagnostic groups using linear mixed-effects model. MAIN OUTCOME MEASURES: Change rates of macula GCC thickness and superficial macula vessel density. RESULTS: Significant mean rates of both GCC thinning and macula vessel density loss were detectable in OHT and GON groups. 49.1% of the individual suspect eyes showed significant loss (P0.2). Higher mean intraocular pressure during follow-up was associated with a faster rate of GCC thinning in the OHT group (P=0.065) and GON groups (P=0.015), but was not associated with the rate of vessel density decrease. CONCLUSIONS: While the rate of GCC thinning was faster on average in suspect eyes than in healthy eyes, some suspect eyes had significant loss of vessel density and faster vessel density loss than GCC thinning. OCT and OCTA are complementary and useful for evaluating eyes with OHT or GON.

PurposeTo investigate the characteristics and rate of central visual field loss after optic disc hemorrhage (DH).DesignProspective cohort study.MethodsThree hundred forty-three eyes of 220 subjects who had ≥3 years of follow-up with a minimum of 5 visits with 10-2 and 24-2 visual field (VF) were recruited. Rates of 10-2 mean deviation (MD) loss in each hemifield and predefined zones were compared using linear mixed-effects models in DH and non-DH eyes. Clustered pointwise regression analysis was also used to define central VF progressors and compared with 24-2 VF loss using guided progression analysis.ResultsThirty-nine eyes with DH and 304 eyes without DH had a mean follow-up of 5.2 years. Eyes with DH had rates of 10-2 MD loss that were 3 times faster than non-DH eyes (mean difference -0.36 dB/year [95% confidence interval 0.54-0.18]; P < .001) and were 3.7 times more likely to progress (P=.002). A larger proportion of glaucomatous eyes showed central VF progression rather than peripheral VF progression in the DH group (30.8% vs. 20.5%) compared with the non-DH group (10.9% vs. 9.2%). In early glaucoma, the rate of 10-2 MD loss was 5.5 times faster in DH eyes than in non-DH eyes (P < .001). Superonasal and superotemporal central VF regions progressed more rapidly than other regions, especially in DH eyes.ConclusionCentral VF loss is accelerated in glaucoma eyes with DH and it corresponds topographically to the DH location. In patients with glaucoma with DH, one should consider supplementing 10-2 VFs with 24-2 VFS to monitor the disease.

PURPOSE: To compare spectral-domain optical coherence tomography (SDOCT) measured circumpapillary retinal nerve fiber layer (cpRNFL) among four glaucomatous optic disc phenotypes in early glaucoma. DESIGN: Clinical cohort study METHODS: In this study, 218 early glaucoma eyes that had at least 3 years of follow-up and a minimum of 4 SDOCT scans were recruited. The optic discs were classified into four types based on appearance: 76 generalized cup enlargement (GE), 53 focal ischemic (FI), 22 myopic glaucomatous (MY), and 67 senile sclerotic (SS). A linear mixed-effect model was used to compare the rates of global and regional cpRNFL thinning among optic disc phenotypes. RESULTS: After adjusting for confounders, the SS group (mean (95% CI): −1.01 (−1.30, −0.73) μm/year) had the fastest mean rate of global cpRNFL thinning followed by FI (−0.77 (−0.97, −0.57) μm/year), MY (0.59 (−0.81, −0.36) μm/year) and GE (−0.58 (−0.75, −0.40) μm/year) at p

PurposeTo examine the epidemiology and factors of cannabis use among open-angle glaucoma (OAG) patients.MethodsIn this cross-sectional study, OAG participants in the All of Us database were included. Cannabis ever-users were defined based on record of cannabis use. Demographic and socioeconomic data were collected and compared between cannabis ever-users and never-users using Chi-Square tests and logistic regression. Odds ratios (OR) of potential factors associated with cannabis use were examined in univariable and multivariable models.ResultsAmong 3723 OAG participants, 1436 (39%) were cannabis ever-users. The mean (SD) age of never-users and ever-users was 72.9 (10.4) and 69.2 (9.6) years, respectively (P&nbsp

Water injection into near dew point gas condensate reservoirs is a common method to delay the condensate dropout near the wellbore. Also water can be injected as waste water disposal into the depleted gas reservoirs or to increase the oil recovery in primary enhanced oil recovery process. All of these processes result in mixing of incompatible injection and formation waters which finally causes mineral scale formation. Gypsum is one of the most common mineral scales which is precipitated uring the mixing of incompatible waters in porous media. This scale can reduce the reservoir rock permeability which affects the success of continuous water injection in hydrocarbon reservoirs. The mineral scale formation through the porous media can be determined if the suitable dispersion coefficient is estimated. Dispersion coefficient is already estimated by neglecting the effects of porous media or using unsuitable tracers which might affect the rate of scale precipitation. Two main issues have been investigated in this work. The first one is the development of an experimental method to measure the dispersion coefficient by a proper tracer which has no interaction with the other ions in porous media. The second one is modeling the concentrations of ions in porous media by two approaches. In this study the standard diffusivity equation and the capacitance approach are used to model the concentration profiles for all ions. The results of this work suggest the application of the capacitance model for the heterogeneous rocks and the standard diffusivity model for the homogeneous ones.

Water injection to reservoirs for recovery increase is a common enhanced oil recovery method in petroleum industry. Water injection might give a negative result due to scale formation and inducing damage in porous media. The compatibility study of mixed waters should be done before deciding about the water injection in reservoir. The time required for the mixture of incompatible waters to reach the maximum potential of scale at desired condition of temperature and pressure is not fully discussed in literature but it is very crucial and is highly dependent to crystallization process. This work may be proved to be of great value in understanding the crystallization process of calcium sulfate due to mixing of formation and injection waters by experimental approach. To simulate the effect of fluid velocity in porous media on the amount of precipitated scale, the experiments are done at two condition of not agitated as well as agitated one. Three zones at which primary nucleation, crystal growth or secondary nucleation controls the scale precipitation has been determined by measuring the amount of scale at different times. The results show that agitation and increasing temperature altogether have an important role on crystallization and reduction of the reaction time required to get the final potential of produced scale. The changes in crystal size and the type of precipitated scale due to temperature increase and agitation were also studied by SEM and EDX altogether at different time duration. Determination of the required velocity of injection in dynamic tests, kinetic of crystallization happening and the change in crystal size of calcium sulfate at different time duration are some of the applications of the results of this work.