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To test the hypothesis that macular ganglion cell layer (GCL) measurements detect early glaucoma with higher accuracy than ganglion cell/inner plexiform layer (GCIPL) thickness measurements.Cross-sectional study.The first cohort included 58 glaucomatous eyes with visual field mean deviation (MD) ≥ -6 dB and 125 normal eyes. The second cohort included 72 glaucomatous and 73 normal/glaucoma suspect (GS) eyes with scans able to create GCL/GCIPL deviation maps.In the first cohort, 8 × 8 GCL and GCIPL grids were exported and 5 superior and inferior sectors were defined. Global and sectoral GCL and GCIPL measures were used to predict glaucoma. In the second cohort, proportions of scan areas with abnormal (5% and1% cutoffs) and supernormal (95% and99% cutoffs) thicknesses on deviation maps were calculated. The extents of GCL and GCIPL abnormal areas were used to predict glaucoma.Extents of abnormal GCL/GCIPL regions and areas under receiver operating characteristic curves (AUROC) for prediction of glaucoma were compared between GCL or GCIPL measures.The average ± standard deviation MDs were -3.7 ± 1.6 dB and -2.7 ± 1.8 dB in glaucomatous eyes in the first and second cohorts, respectively. Global GCIPL thickness measures (central 18° × 18° macular region) performed better than GCL for early detection of glaucoma (AUROC, 0.928 vs. 0.884, respectively; P = 0.004). Superior and inferior sector 3 thickness measures provided the best discrimination with both GCL and GCIPL (inferior GCL AUROC, 0.860 vs. GCIPL AUROC, 0.916 [P = 0.001]; superior GCL AUROC, 0.916 vs. GCIPL AUROC, 0.900 [P = 0.24]). The extents of abnormal GCL regions at a 1% cutoff in the central elliptical area were 17.5 ± 22.2% and 6.4 ± 10.8% in glaucomatous and normal/GS eyes, respectively, versus 17.0 ± 22.2% and 5.7 ± 10.5%, respectively, for GCIPL (P = 0.06 for GCL and 0.002 for GCIPL). The extents of GCL and GCIPL supernormal regions were mostly similar in glaucomatous and normal eyes. The best performance for prediction of glaucoma in the second cohort was detected at a P value of1% within the entire scan for both GCL and GCIPL (AUC, 0.681 vs. 0.668, respectively; P = 0.29).Macular GCL and GCIPL thicknesses are equivalent for identifying early glaucoma with current OCT technology. This is likely explained by limitations of inner macular layer segmentation and concurrent changes within the inner plexiform layer in early glaucoma.

We describe a method that provides rapid visualization of glaucomatous change in a 2-dimensional (2D) structural and functional (S/F) space.To describe a method to visualize glaucomatous change in a 2D S/F space.This was a retrospective longitudinal observational study.Group I included 64 normal and 64 glaucomatous eyes used to develop the structural score. Group II included 957 glaucomatous eyes used to plot the structural-functional progression vectors.Subjects were arranged in 2 groups. Group I was a cross-sectional group used to develop a structural score which were applied to longitudinal measurements of patients in group II for vectoral analysis. Visual field index was used as a functional score. Vectors were created for each eye to define structural (x) and functional (y) progression. The structural and functional components were calculated with linear models of optical coherence tomography scores and visual field index. The resultant vector and its confidence interval were plotted in 2D S/F space.Combined structural-functional glaucomatous progression.Group I included 64 normal and 64 glaucomatous eyes. We calculated 957 vectors (957 eyes of 582 OAG patients) in group II. The mean (±SD) follow-up period was 6.9 (±1.5) years and mean baseline mean deviation (MD) was -4.3 (±5.4). Preperimetric, mild, moderate, and severe groups included 159, 288, 299, and 211 eyes, respectively. Mean baseline MDs in these groups were 0.8, -1.0, -3.7, and -11.2 dB, and mean vector slopes were 0.88, 1.00, 1.98, and 2.69.We present a method that presents glaucoma progression in a 2D S/F space. This approach integrates a large amount of longitudinal numerical data and provides the clinician with a rapid and intuitive summary of the patient's glaucoma trajectory.

PurposeWe compared ganglion cell layer (GCL) and inner plexiform layer (IPL) rates of change (RoC) in patients with glaucoma suspect (GS) and established glaucoma (EG) to test the hypothesis that IPL thickness changes would occur earlier than GCL changes in eyes with early damage.DesignProspective, cohort study.MethodsA total of 64 GS eyes (46 patients) and 112 EG eyes (112 patients) with ≥2 years of follow-up and ≥3 macular optical coherence tomography scans were included. GCL and IPL superpixel thickness measurements were exported. A Bayesian hierarchical model with random intercepts/slopes and random residual variances was fitted to estimate RoC in individual superpixels. Normalized RoC and proportions of superpixels with significantly negative and positive GCL and IPL RoC were compared within the groups.ResultsThe average (SD) follow-up time and number of scans were 3.5 (0.7) years and 4.2 (1.0), respectively, in the GS group and 3.6 (0.4) years and 7.3 (1.1) in the EG group. Mean (SD) normalized RoC was faster for GCL than IPL (-0.69 [0.05] vs -0.33 [0.04]) in the GS group, whereas it was faster for IPL (-0.47 [0.03] vs -0.28 [0.02]) in EG eyes. GCL RoC were significantly negative in 24 of 36 superpixels compared with 8 of 36 for IPL (P < .001) in GS eyes. In the EG group, 23 of 36 superpixels had significant negative IPL RoC compared with 13 of 36 superpixels for GCL (P=.006).ConclusionsGCL thickness is more likely to demonstrate change over time compared with IPL in glaucoma suspects. There is no evidence of preferential IPL thinning in eyes with suspected early glaucoma damage.

To develop a structural metascore (SMS) that combines measurements from different devices and expresses them on a single scale to facilitate their long-term analysis.Three structural measurements (Heidelberg Retina Tomograph II [HRT] rim area, HD-Cirrus optical coherence tomography [OCT] average retinal nerve fiber layer [RNFL] thickness, Spectralis OCT RNFL global thickness) were normalized on a scale of 0 to 100 and converted to a reference value. The resultant metascores were plotted against time. SMS performance was evaluated to predict future values (internal validation), and correlations between the average grades assigned by three clinicians were compared with the SMS slopes (external validation).The linear regression fit with the variance approach, and adjustment to a Spectralis equivalent was the best-performing approach; this was denominated metascore. Plots were created for 3416 eyes of 1824 patients. The average baseline age (± standard deviation) was 69.8 (±13.9), mean follow-up was 11.6 (±4.7) years, and mean number of structural scans per eye was 10.0 (±4.7). The mean numbers of scans per device were 3.8 (±2.5), 5.0 (±2.9), and 1.3 (±3.0) for HRT, Cirrus, and Spectralis, respectively. The metascore slopes' median was -0.3 (interquartile range 1.1). Correlations between the average grades assigned by the three clinicians and the metascore slopes were -0.51, -0.49, and -0.69 for the first (structural measurement printouts alone), second (metascore plots alone), and third (printouts + metascore plots) series of gradings, respectively. The average absolute predictive ability was 7.63/100 (whereas 100 = entire normalized scale).We report a method that converts Cirrus global RNFL and HRT global rim area normalized measurements to Spectralis global RNFL equivalent values to facilitate long-term structural follow-up.Because glaucoma changes usually occur slowly, patients are often examined with different instruments during their follow-up, a method that "unifies" structural measurements provided by different devices, which could assist patients' longitudinal structural follow-up.

PurposeTo test the hypothesis that newly developed shape measures using optical coherence tomography (OCT) macular volume scans can discriminate patients with perimetric glaucoma from healthy subjects.MethodsOCT structural measures defining macular topography and volume were recently developed based on cubic Bézier curves. We exported macular volume scans from 135 eyes with glaucoma (133 patients) and 155 healthy eyes (85 subjects) and estimated global and quadrant-based measures. The best subset of measures to predict glaucoma was explored with a gradient boost model (GBM) with subsequent logistic regression. Accuracy and area under receiver operating curves (AUC) were the primary metrics. In addition, we separately investigated model performance in 66 eyes with mild glaucoma (mean deviation ≥ -6dB).ResultsAverage (±SD) 24-2 mean deviation was -8.2 (±6.1) dB in eyes with glaucoma. The main predictive measures for glaucoma were temporal inferior rim height, nasal inferior pit volume, and temporal inferior pit depth. Lower values for these measures predicted higher risk of glaucoma. Sensitivity, specificity, and AUC for discriminating between healthy and glaucoma eyes were 81.5% (95% CI=76.6-91.9%), 89.7% (95% CI=78.7-94.2%), and 0.915 (95% CI=0.882-0.948), respectively. Corresponding metrics for mild glaucoma were 84.8% (95% CI=72.1%-95.5%), 85.8% (95% CI=87.1%-97.4%), and 0.913 (95% CI=0.867-0.958), respectively.ConclusionsNovel macular shape biomarkers detect early glaucoma with clinically relevant performance. Such biomarkers do not depend on intraretinal segmentation accuracy and may be helpful in eyes with suboptimal macular segmentation.Translational relevanceMacular shape biomarkers provide valuable information for detection of early glaucoma and may provide additional information beyond thickness measurements.

Rbfox1 is a multifunctional RNA-binding protein that regulates alternative splicing, transcription, mRNA stability, and translation. Rbfox1 is an important regulator of gene networks involved in neurogenesis and neuronal function. Disruption of Rbfox function has been associated with several neurodevelopmental and neuropsychiatric disorders. We have shown earlier that Rbfox1 is expressed in retinal ganglion and amacrine cells (ACs) and that its down-regulation in adult mouse retinas leads to deficiency of depth perception. In the present study, we used several markers of ACs, including gamma-aminobutyric acid (GABA), choline acetyltransferase (ChAT), neuropeptide Y (NPY), glycine transporter (GlyT1), and vesicular glutamate transporter 3 (VGlut3) to identify types of ACs that express Rbfox1. Expression of Rbfox1 was observed predominantly in GABAergic ACs located in the inner nuclear layer (INL) and ganglion cell layer (GCL). All GABAergic/cholinergic starburst ACs and virtually all NPY-positive GABAergic ACs were also Rbfox1-positive. Among glycinergic ACs, a sparse population of Rbfox1/VGlut3-positive cells was identified, indicating that Rbfox1 is expressed in a very small population of glycinergic ACs. These data contribute to our understanding about molecular differences between various types of amacrine cells and the cell-specific gene networks regulated by Rbfox1.

Purpose Most reports of strabismus after glaucoma drainage device implantation study larger devices and rarely note the incidence of strabismus after Ahmed glaucoma valve (AGV) implantation. It is unknown if the pattern of strabismus is similar with smaller devices. We investigated characteristics of strabismus after AGV implantation. Design Retrospective review. Methods Institutional study of 732 patients at our institution undergoing AGV implantation between 2013 and 2018. Rate and characteristics of strabismus were the primary outcome; age, gender, and location of AGVs were also analyzed. Results We identified 29 patients who developed new-onset strabismus postoperatively after initial AGV implantation, for 4% incidence of strabismus. Twenty-one (72%) of these had diplopia. AGVs were implanted superotemporally in 21, superonasally in 5, inferotemporally in 1, and inferonasally in 2. Three patients were esotropic, 11 were exotropic, 4 had hypertropia, 2 had hypotropia, and 9 patients had combined horizontal/vertical strabismus (esotropia/hypotropia [n = 1] or exotropia/hypertropias [n = 8]). Exotropia was the most common type of strabismus in both the superotemporal and superonasal (60%) AGV groups. Superotemporal AGVs were more commonly associated with ipsilateral hypertropia (43%) than superonasal AGVs. Treatments included strabismus surgery (n = 14), prisms (n = 6), or an occlusive lens (n = 1). Discussion. In the largest single-center series of patients undergoing initial AGV implantation, the overall incidence of postoperative strabismus was 4%. This is comparable to strabismus incidence following implantation of other types of glaucoma drainage devices, even larger devices. The possibility of this complication should be discussed with patients prior to surgery.

PurposeAccurate neural rim measurement based on optic disc imaging is important to glaucoma severity grading and often performed by trained glaucoma specialists. We aim to improve upon existing automated tools by building a fully automated system (RimNet) for direct rim identification in glaucomatous eyes and measurement of the minimum rim-to-disc ratio (mRDR) in intact rims, the angle of absent rim width (ARW) in incomplete rims, and the rim-to-disc-area ratio (RDAR) with the goal of optic disc damage grading.DesignRetrospective cross sectional study.ParticipantsOne thousand and twenty-eight optic disc photographs with evidence of glaucomatous optic nerve damage from 1021 eyes of 903 patients with any form of primary glaucoma were included. The mean age was 63.7 (± 14.9) yrs. The average mean deviation of visual fields was-8.03 (± 8.59).MethodsThe images were required to be of adequate quality, have signs of glaucomatous damage, and be free of significant concurrent pathology as independently determined by glaucoma specialists. Rim and optic cup masks for each image were manually delineated by glaucoma specialists. The database was randomly split into 80/10/10 for training, validation, and testing, respectively. RimNet consists of a deep learning rim and cup segmentation model, a computer vision mRDR measurement tool for intact rims, and an ARW measurement tool for incomplete rims. The mRDR is calculated at the thinnest rim section while ARW is calculated in regions of total rim loss. The RDAR was also calculated. Evaluation on the Drishti-GS dataset provided external validation (Sivaswamy 2015).Main outcome measuresMedian Absolute Error (MAE) between glaucoma specialists and RimNet for mRDR and ARW.ResultsOn the test set, RimNet achieved a mRDR MAE of 0.03 (0.05), ARW MAE of 31 (89)°, and an RDAR MAE of 0.09 (0.10). On the Drishti-GS dataset, an mRDR MAE of 0.03 (0.04) and an mRDAR MAE of 0.09 (0.10) was observed.ConclusionsRimNet demonstrated acceptably accurate rim segmentation and mRDR and ARW measurements. The fully automated algorithm presented here would be a valuable component in an automated mRDR-based glaucoma grading system. Further improvements could be made by improving identification and segmentation performance on incomplete rims and expanding the number and variety of glaucomatous training images.

Purpose To present a method that allows visualization of functional and structural change in 2-dimensional space. Design Retrospective, longitudinal, observational study. Participants Patients from the Stein Eye Institute, UCLA from 1993 through 2017. Methods Patients were arranged into 2 cohorts. Cohort 1 was used to create a structural score for the horizontal axis of the structural–functional (S-F) 2-dimensional space. The visual field (VF) index was used for the vertical axis as the functional score. Cohort 2 was used to apply those scores for analysis of S-F progression with a combined vector. The first cohort included eyes with mild glaucoma (abnormal glaucoma hemifield test results, pattern standard deviation –5 dB) and normal control participants. The second cohort included all stages of open-angle glaucoma with ≥5 OCT retinal nerve fiber layer scans, ≥5 reliable visual field (VF) results, and follow-up of ≥4 years. Main Outcome Measures Vectors were created for each eye to represent the trajectory of glaucoma progression over time. Each vector was defined by structural (x-axis) and functional (y-axis) components. The structural component was calculated with a linear model of Heidelberg Retina Tomograph (Heidelberg Engineering, Heidelberg, Germany) scores over time. The functional component was calculated with a linear model of VF measurements over time. The resultant vector and its confidence interval were plotted in 2-dimensional S-F space. Eyes were divided into severity stages based on baseline MD. A mean vector was calculated for each severity stage. Results We obtained 290 vectors from 290 eyes of 196 patients. The mean ± standard deviation follow-up period was 14.6±3.1 years. Average age was 58.6±8.8 years. Preperimetric, mild, moderate, and severe categories included 41, 89, 97, and 63 eyes, respectively. Mean baseline MDs were 0.8 dB, –0.95 dB, –3.57 dB, and –11.51 dB, respectively, and mean vector slopes for each severity categories were 0.79, 0.95, 1.95, and 2.08, respectively. Cook’s distance removed 131 (7.1%) and 137 (7.4%) outliers from the structure and function regressions, respectively. Conclusions We report a method to visualize the trajectory of a patient’s glaucoma progression in a 2-dimensional S-F space. The slope of the trajectory of glaucoma progression is a function of the severity of the disease.

PURPOSE: To investigate the relationship between longitudinal changes in macular thickness measurements from optical coherence tomography (OCT) and changes in central visual field (VF) in glaucoma patients with central or advanced damage at baseline. DESIGN: Longitudinal cohort study. SUBJECTS: 116 eyes with ≥3 years of follow-up and ≥5 macular OCT images and central 10° VF tests were selected. METHODS: OCT superpixels and VF locations were matched correcting for retinal ganglion cell displacement. Superpixel thickness and visual field (VF) total deviation (TD) values, in both logarithmic and linear scales, were averaged within 3 eccentricities (3.4°, 5.6°, and 6.8°) and superior and inferior he miretinas and hemifields. We estimated pointwise TD rates of change and rates of change at superpixels for full macular thickness (FMT), ganglion cell complex (GCC), ganglion cell-inner plexiform layer (GCIPL) and ganglion cell layer (GCL). Correlation of structural and functional (SF) rates of change were investigated with parametric tests. We compared the proportion of worsening and positive slopes for superpixels and VF test locations (negative vs. positive rates of change with p

To identify predictive factors for visual field (VF) fluctuation in glaucoma patients.Retrospective cohort study.A total of 1392 eyes (816 patients) with 6 or more VFs and 3 years or more of follow-up.For each eye, the VF mean deviation (MD) and the pointwise sensitivities were regressed against time to model the series trend, and the root mean square error (RMSE) was estimated as a measure of variability. Potential predictors were selected with least absolute shrinkage and selection operator regression and included eye laterality, ethnicity, glaucoma type, intraocular pressure (IOP) fluctuation, baseline best corrected-visual acuity, intervening cataract or glaucoma surgery, length of follow-up, frequency of testing, baseline MD, rates of VF progression, and median false positive (FP) and false negative (FN) responses.Predictors of global and pointwise VF long-term fluctuation.In the global model, left eye (0.063 dB; P = 0.022), Asian descent (0.265 dB; P = 0.006), larger IOP fluctuation (0.051 dB; P0.001), intervening cataract surgery (0.090 dB; P = 0.023), longer follow-up (0.130 dB; P0.001), worse baseline MD (-0.145 dB; P0.001), faster VF decay rate (-0.090 dB; P0.001), and higher FP rate (0.145 dB; P0.001) and FN rate (0.220 dB; P0.001) were predictors of VF fluctuation. In the pointwise model, larger IOP fluctuation (0.039 dB; P = 0.022), longer follow-up (0.340 dB; P0.001), higher VF frequency (0.238 dB; P = 0.002), intervening glaucoma surgery (0.190 dB; P = 0.01), worse baseline MD (-0.535 dB; P0.001), faster VF decay rate (-0.340 dB; P0.001), and higher FP rate (0.255 dB; P0.001) and FN rate (0.395 dB; P0.001) were associated with increased fluctuation. The multivariable model explained 57% and 28% of the pointwise and global variances, respectively.This study identified novel predictors of VF fluctuation, and explains nearly 60% of the pointwise variance. In the presence of factors predictive of high fluctuation, increased frequency of testing and better analytics will help to identify VF progression more accurately.

PURPOSE The purpose of this study was to evaluate the efficacy of intraocular pressure (IOP) control after combined CyPass Micro-Stent implantation and cataract surgery (combined surgery). METHODS All cases of combined surgery performed from February 2017 to July 2018 at Stein and Doheny Eye Institutes were reviewed. The primary outcome was a qualified success with stratified IOP targets based on criteria: final IOP (A) ≤18 mm Hg and reduction of 20%, (B) ≤15 mm Hg and reduction of 25%, (C) ≤12 mm Hg and reduction of 30%. Secondary outcome measures included postoperative IOP and number of medications, complications, additional glaucoma surgery, and postoperative refractive error. Predictive factors for failure were investigated. IOP spike was defined as a postoperative IOP ≥30 or >10 mm Hg increase from preoperative IOP. RESULTS One hundred forty-one eyes (107 patients) were included. Mean (±SD) preoperative IOP was 15.4±3.4 mm Hg on an average of 2.2±1.1 medications. A statistically significant reduction in IOP and number of medications was seen at 12 months (13.8±4.2 mm Hg, 1.3±1.3 medications, P

BackgroundTo evaluate the relationship between the presence of an acquired pit of the optic nerve (APON) and the rate of visual field (VF) decay in primary open-angle glaucoma (POAG).MethodsConsecutive patients with POAG were screened for APON by three glaucoma specialists. A control group of POAG eyes without APON were matched with the APON group for factors such as age, gender, baseline intraocular pressure and baseline mean deviation (MD). The pointwise rate of change (PRC) was used for pointwise comparisons between the two groups. MD rate, Visual Field Index (VFI) rate and Glaucoma Rate Index (GRI) were used for global rate comparisons. We compared the proportions of eyes progressing in the groups with event-based guided progression analysis (GPA), MD, VFI and GRI criteria.ResultsMean (SD) PRC was faster in the APON group −1.00 (±2.57) %/year compared with the control group −0.25 (±2.19) %/year; p0.1).ConclusionsThe presence of APON in patients with POAG is associated with focal, fast rates of VF decay. Identification of patients with APON should alert clinicians to the possibility of a fast rate of functional progression and to consider appropriately aggressive treatment of their glaucoma.

ImportanceThere are scarce data on the association of blood pressure measures with subsequent macular structural rates of change in patients with glaucoma.ObjectiveTo investigate the association of baseline blood pressure measures with rates of change of the macular ganglion cell complex in patients with central or moderate to advanced glaucoma damage at baseline.Design, Setting, and ParticipantsThis prospective cohort study, conducted from August 2021 to August 2022, used data from patients in the Advanced Glaucoma Progression Study at the University of California, Los Angeles. Participants were between 39 and 80 years of age and had more than 4 macular imaging tests and 2 or more years of follow-up.ExposuresA diagnosis of glaucoma with either central damage or a visual field mean deviation worse than −6 dB.Main Outcomes and MeasuresThe main outcome was the association of blood pressure measures with ganglion cell complex rates of change. Macular ganglion cell complex thickness rates of change were estimated with a bayesian hierarchical model. This model included relevant demographic and clinical factors. Blood pressure measures, intraocular pressure, and their interactions were added to the model to assess the association of baseline blood pressure measures with global ganglion cell complex rates of change.ResultsThe cohort included 105 eyes from 105 participants. The mean (SD) age, 10-2 visual field mean deviation, and follow-up time were 66.9 (8.5) years, –8.3 (5.3) dB, and 3.6 (0.4) years, respectively, and 67 patients (63.8%) were female. The racial and ethnic makeup of the cohort was 15 African American (14.3%), 23 Asian (21.9%), 12 Hispanic (11.4%), and 55 White (52.4%) individuals based on patient self-report. In multivariable analyses, female sex, history of taking blood pressure medications, higher intraocular pressure, thicker central corneal thickness, shorter axial length, higher contrast sensitivity at 12 cycles per degree, and higher baseline 10-2 visual field mean deviation were associated with faster ganglion cell complex thinning. Lower diastolic blood pressure was associated with faster rates of ganglion cell complex thinning at higher intraocular pressures. For intraocular pressures of 8 and of 16 mm Hg (10% and 90% quantiles, respectively), every 10 mm Hg–lower increment of diastolic blood pressure was associated with 0.011 μm/y slower and –0.130 μm/y faster rates of ganglion cell complex thinning, respectively.Conclusions and RelevanceIn this cohort study, a combination of lower diastolic blood pressure and higher intraocular pressure at baseline was associated with faster rates of ganglion cell complex thinning. These findings support consideration of evaluating and addressing diastolic blood pressure as a therapeutic measure in patients with glaucoma if supported by appropriate clinical trials.

PurposeTo test the hypothesis that macular ganglion cell complex (GCC) thickness from optical coherence tomography (OCT) provides a stronger change signal regardless of glaucoma severity compared with other macular measures.DesignProspective cohort study.MethodsEyes were from 112 patients with moderate to severe glaucoma at baseline from a tertiary glaucoma center. In each 3°×3° macular superpixel, a hierarchical Bayesian random intercept and slope model with random residual variance was fit to longitudinal full macular thickness (FMT), outer retina layers, GCC, ganglion cell-inner plexiform layer (GCIPL), and ganglion cell layer (GCL) measurements. We estimated population- and individual-level slopes and intercepts. Proportions of substantial worsening and improving superpixel slopes were compared between layers and in superpixels with mild to moderate vs severe damage (total deviation of corresponding visual field location ≥ -8 vs < -8 dB).ResultsMean (SD) follow-up time and baseline 10-2 visual field mean deviation were 3.6 (0.4) years and -8.9 (5.9) dB, respectively. FMT displayed the highest proportion of significant negative slopes (1932/3519 [54.9%]), followed by GCC (1286/3519 [36.5%]), outer retina layers (1254/3519 [35.6%]), (GCIPL) (1075/3518 [30.6%]), and (GCL) (698/3518 [19.8%]). Inner macular measures detected less worsening in the severe glaucoma group; yet GCC (223/985 [22.6%]) identified the highest proportion (GCIPL: 183/985 [18.6%]; GCL: 106/985 [10.8%]). Proportions of positive rates were small and comparable among all measures.ConclusionsGCC is the optimal macular measure for detection of structural change in eyes with moderate to severe glaucoma. Although a higher proportion of worsening superpixels was observed for FMT, a large portion of FMT change could be attributed to changes in outer retina layers.

Management of concomitant cataract and glaucoma depends on the stage of glaucoma and the patient's situation. There are different surgical options for handling visually significant cataract and mild-to-moderate open-angle glaucoma (OAG). We aimed to compare the one-year results of phacoemulsification alone versus phacoviscocanalostomy in these patients.This was a parallel-arm, single-masked, randomized-controlled trial, conducted at Farabi Eye Hospital, Tehran, Iran between January 2016 and January 2018. We enrolled 89 eyes from 89 patients with mild-to-moderate primary OAG or pseudoexfoliative glaucoma (PEXG) with visually significant age-related cataract. They randomly underwent phacoemulsification alone (n = 44) or combined phaco-viscocanalostomy (n = 45). All patients had a 12-month follow-up period, and the mean intraocular pressure (IOP), the number of antiglaucoma medications, and complete and qualified success rates were compared.After the 1st and 3rd months, the mean IOP showed significantly decreased in the phaco-visco group compared to the phaco group (P 0001 and P = 0.004, respectively), but it was not statistically significant at 6th and 12th months (P = 0.540 and P = 0.530). The need for antiglaucoma medication and the complete and qualified success rates were significantly in favour of the phaco-visco group in all postoperative visits (P 0.05).Although both phacoemulsification alone and phacoviscocanalostomy procedures can be considered for patients with mild-to-moderate OAG, we found better success rates using phacoviscocanalostomy. Therefore, if the surgeon is an expert in performing this technique, this non-penetrating procedure can be applied in patients with visually significant cataract and earlier stages of OAG, especially in patients with PEXG.

To investigate spatiotemporal correlations among ganglion cell complex (GCC) superpixel thickness measurements and explore underlying patterns of longitudinal change across the macular region.Longitudinal cohort study.One hundred eleven eyes from 111 subjects from the Advanced Glaucoma Progression Study with ≥ 4 visits and ≥ 2 years of follow-up.We further developed our proposed Bayesian hierarchical model for studying longitudinal GCC thickness changes across macular superpixels in a cohort of glaucoma patients. Global priors were introduced for macular superpixel parameters to combine data across superpixels and better estimate population slopes and intercepts.Bayesian residual analysis to inspect cross-superpixel correlations for subject random effects and residuals. Principal component analysis (PCA) to explore underlying patterns of longitudinal macular change.Average (standard deviation [SD]) follow-up and baseline 10-2 visual field mean deviation were 3.6 (0.4) years and -8.9 (5.9) dB, respectively. Superpixel-level random effects and residuals had the greatest correlations with nearest neighbors; correlations were higher in the superior than in the inferior region and strongest among random intercepts, followed by random slopes, residuals, and residual SDs. PCA of random intercepts showed a first large principal component (PC) across superpixels that approximated a global intercept, a second PC that contrasted the superior and inferior macula, and a third PC, contrasting inner and nasal superpixels with temporal and peripheral superpixels. PCs for slopes, residual SDs, and residuals were remarkably similar to those of random intercepts.Introduction of cross-superpixel random intercepts and slopes is expected to improve estimation of population and subject parameters. Further model enhancement may be possible by including cross-superpixel random effects and correlations to address spatiotemporal relationships in longitudinal data sets.

To investigate the retinal proteins associated with primary and secondary retinal ganglion cell (RGC) degeneration and explore their molecular pathways, SWATH label-free and target-based mass spectrometry was employed to identify the proteomes in various retinal locations in response to localized optic nerve injury. Unilateral partial optic nerve transection (pONT) was performed on adult Wistar rats and their retinas were harvested 2 weeks later. To confirm the separation of primary and secondary RGC degeneration, immunohistochemistry of RNA binding protein with multiple splicing (RBPMS) and glial fibrillary acidic protein (GFAP) was performed on retinal whole-mounts. Retinal proteomes in the temporal and nasal quadrants were evaluated with high resolution hybrid quadrupole time-of-flight mass spectrometry (QTOF-MS), and SWATH-based acquisition, and their expression was compared to the corresponding retinal quadrant in contralateral control eyes and further validated by multiple reaction monitoring mass spectrometry (MRM-MS). A total of 3641 proteins (FDR &lt, 1%) were identified using QTOF-MS. The raw data are available via ProteomeXchange with the identifier PXD026783. Bioinformatics data analysis showed that there were 37 upregulated and 25 downregulated proteins in the temporal quadrant, whereas 20 and five proteins were upregulated and downregulated, respectively, in the nasal quadrant, respectively (n = 4, p &lt, 0.05, fold change ≥ 1.4-fold or ≤0.7). Six proteins were regulated in both the temporal and the nasal quadrants, including CLU, GFAP, GNG5, IRF2BPL, L1CAM, and CPLX1. Linear regression analysis indicated a strong association between the data obtained by means of SWATH-MS and MRM-MS (temporal, R2 = 0.97, nasal, R2 = 0.96). Gene ontology analysis revealed statistically significant changes in the biological processes and cellular components of primary RGC degeneration. The majority of the significant changes in structural, signaling, and cell death proteins were associated with the loss of RGCs in the area of primary RGC degeneration. The combined use of SWATH-MS and MRM-MS methods detects and quantifies regional changes of retinal protein expressions after localized injury. Future investigation with this integrated approach will significantly increase the understanding of diverse processes of progressive RGC degeneration from a proteomic prospective.

Background/aimsTo identify clinical characteristics and factors associated with microcystic macular edema (MME) in patients with primary open-angle glaucoma (POAG).MethodsWe included 315 POAG eyes between 2010 and 2019 with good-quality macular volume scans that had reliable visual fields (VF) available within 6 months in this observational retrospective cohort study. Eyes with retinal pathologies except for epiretinal membrane (ERM) were excluded. The inner nuclear layer was qualitatively assessed for the presence of MME. Global mean deviation (MD) and Visual Field Index (VFI) decay rates, superior and inferior MD rates and pointwise total deviation rates of change were estimated with linear regression. Logistic regression was performed to identify baseline factors associated with the presence of MME and to determine whether MME is associated with progressive VF loss.Results25 out of 315 eyes (7.9%) demonstrated MME. The average (±SD) age and MD in eyes with and without MME was 57.2 (±8.7) versus 62.0 (±9.9) years (p=0.02) and −9.8 (±5.7) versus −4.9 (±5.3) dB (p0.49).ConclusionsMore severe glaucoma and younger age were associated with MME. MME was not associated with faster global VF decay in this cohort. MME may confound monitoring of glaucoma with full macular thickness.

Purpose To test the hypothesis that baseline optical coherence tomography (OCT) measures predict visual field (VF) progression in a cohort of patients with suspected or established glaucoma and to compare their performance to semiquantitative optic disc measures. Design This was an observational cohort study. Methods The setting of this study was an academic institution. The study population included 171 eyes of 95 patients with good-quality baseline retinal nerve fiber layer (RNFL) and macular OCT images and disc photographs with >2 years of follow-up and ≥5 VFs. The observation procedures were baseline macular and RNFL OCT measures and cup-to-disc ratio and disc damage likelihood score. The main outcome measure was prediction of glaucomatous VF deterioration according to trend and event analyses. Results Median (interquartile range) baseline mean deviation and follow-up were -2.9 (-6.4 to -1.1) dB and 54 (44–65) months, respectively. Seventeen and 25 eyes progressed by final visit based on pointwise event analysis and trend analysis of visual field index (VFI), respectively. Thinner central corneal thickness (P = .005), female gender (P = .015), and thinner average peripapillary RNFL (P = .001) predicted VF progression on proportional hazard models. Thinner RNFL at baseline (P = .006) or thinner average ganglion cell-inner plexiform layer (P = .028) along with higher baseline VFI (P = .018 and .048, respectively) predicted VFI progression. Neither optic disc measures predicted VF progression in any of the explored models. Conclusions Baseline structural OCT measures predicted subsequent VF progression in contrast to semi-quantitative optic disc measures. OCT-based structural measures should be included in prognostic models of glaucomatous VF deterioration.

PurposeTo review central structure-function (SF) relationships in glaucoma; to compare contributions of within-session and between-session variability to total variability of macular optical coherence tomography (OCT) thickness measurements; and to test the hypothesis that longitudinal within-eye variability of central SF relationships is smaller than between-individual variability.MethodsWe reviewed the pertinent literature on central SF relationships in glaucoma. Thirty-eight eyes (20 normal or glaucoma subjects) had×3 macular images per session over 3 sessions, and superpixels thickness measurements for ganglion cell layer (GCL), ganglion cell/inner plexiform layer (GCIPL), ganglion cell complex (GCC), and full macular thickness (FMT) were exported. Linear mixed models were used for estimating contributions of between- and within-session variability to total thickness variability. One hundred twenty eyes with ≥3 10° visual fields (VFs)/OCT images were enrolled for the longitudinal study. We investigated within-eye longitudinal SF relationships (GCIPL thickness vs VF total deviations) with a change-point regression model and compared within-eye to between-individual variabilities with components-of-variance models.ResultsIn the cross-sectional study, the between-session component contributed 8%, 11%, 11%, and 36% of total variability for GCL, GCIPL, GCC, and FMT, respectively. In the longitudinal study, between-individual variability explained 78%, 77%, and 67% of total SF variability at 3.4°, 5.6°, and 6.8° eccentricities, respectively (P < .05). SF relationships remained stable over time within individual eyes.ConclusionsWithin-session variability accounts formost of macular thickness variability over time. Longitudinal within-eye SF variability is smaller than between-individual variability. Study of within-eye SF relationships could help clinicians better understand SF linking in glaucoma and help refine progression algorithms. NOTE: Publication of this article is sponsored bythe American Ophthalmological Society.

Purpose To compare the outcomes of Descemet membrane endothelial keratoplasty (DMEK) with those of Descemet's stripping endothelial keratoplasty (DSEK) in eyes with prior glaucoma surgery. Design Case-matched retrospective comparative case series. Methods Setting/study population: 46 DMEK procedures were matched with 46 DSEK procedures at a single institution. Observation procedures: cases were matched based on preoperative visual acuity, lens status, and surgical indication. Main outcome measurements: the outcome measurements included visual acuity improvement, primary and secondary graft failure, endothelial rejection, intraocular pressure (IOP) elevation, and the need for additional glaucoma intervention. Results Best-corrected visual acuity (BCVA) improved by −0.89 logMAR in the DMEK group and −0.62 logMAR in the DSEK group (P = 0.005) at 1 year follow-up. Visual acuity was significantly better in the DMEK group at postoperative months 1, 3, and 12 and at last follow-up. The percentage of patients achieving 20/40 or better best-corrected visual acuity was higher in the DMEK group at all time points, notably 47% in the DMEK group versus 15% in the DSEK group at 1 year (P = 0.002). Secondary graft failure was lower in the DMEK group (DMEK 0% vs. DSEK 17%; P = 0.006). Primary graft failure rates and rebubling rates were similar. There were no differences in the rates of postoperative IOP elevation or in the need for additional glaucoma intervention. Conclusions In complex eyes with prior glaucoma surgery, DMEK offers faster visual recovery, better final visual acuity, and a lower rate of secondary graft failure compared to DSEK during the first postoperative year and beyond.

To test the hypothesis that cataract surgery slows the apparent rate of visual field (VF) decay in primary open-angle glaucoma patients compared with rates measured during cataract progression.Retrospective cohort study.Consecutive open-angle glaucoma patients who underwent cataract surgery and who had ≥4 VFs and ≥3 years of follow-up before and after surgery were retrospectively reviewed. Mean deviation (MD) rate, visual field index (VFI) rate, pointwise linear regression (PLR), pointwise rate of change (PRC), and the Glaucoma Rate Index (GRI) were compared before and after cataract surgery.A total of 134 eyes of 99 patients were included. Median (interquartile range) follow-up was 6.5 (4.7-8.1) and 5.3 (4.0-7.3) years before and after cataract surgery, respectively. All intraocular pressure (IOP) parameters (mean IOP, standard deviation of IOP, and peak IOP) significantly improved (P.001) after cataract surgery. All VF indices indicated an accelerated VF decay rate after cataract surgery: MD rate (-0.18 ± 0.40 dB/year vs -0.40 ± 0.62 dB/year, P.001), VFI rate (-0.44% ± 1.09%/year vs -1.19% ± 1.85%/year, P.001), GRI (-5.5 ± 10.8 vs -13.5 ± 21.5; P.001), and PRC (-0.62% ± 2.47%/year before and -1.35% ± 3.71%/year after surgery; P.001) and PLR (-0.20 ± 0.82 dB/year before and -0.42 ± 1.16 dB/year after surgery; P.001) for all VF locations. Worse baseline MD and postoperative peak IOP were significantly associated with the postoperative VF decay rate and the change in the decay rate after cataract surgery.Although all IOP parameters improved after cataract surgery, VFs continued to progress. Cataract surgery does not slow the apparent rate of glaucomatous VF decay as compared to rates measured during the progression of the cataract.

PurposeWe compared rates of change of macular ganglion cell/inner plexiform (GCIPL) thickness and proportion of worsening and improving rates from 2 optical coherence tomography (OCT) devices in a cohort of eyes with glaucoma.DesignLongitudinal cohort study.MethodsIn a tertiary glaucoma clinic we evaluated 68 glaucoma eyes with ≥2 years of follow-up and ≥4 OCT images. Macular volume scans from 2 OCT devices were exported, coregistered, and segmented. Global and sectoral GCIPL data from the central 4.8×4.0-mm region were extracted. GCIPL rates of change were estimated with linear regression. Permutation analyses were used to control specificity with the 2.5 percentile cutoff point used to define "true" worsening. Main outcome measures included differences in global/sectoral GCIPL rates of change between 2 OCT devices and the proportion of negative vs positive rates of change (P < .05).ResultsAverage (standard deviation) 24-2 visual field mean deviation, median (interquartile range) follow-up time, and number of OCT images were -9.4 (6.1) dB, 3.8 (3.3-4.2) years, and 6 (5-8), respectively. GCIPL rates of thinning from Spectralis OCT were faster (more negative) compared with Cirrus OCT; differences were significant in superonasal (P=.03) and superotemporal (P=.04) sectors. A higher proportion of significant negative rates was observed with Spectralis OCT both globally and in inferotemporal/superotemporal sectors (P < .04). Permutation analyses confirmed the higher proportion of global and sectoral negative rates of change with Spectralis OCT (P < .001).ConclusionsChanges in macular GCIPL were detected more frequently on Spectralis' longitudinal volume scans than those of Cirrus OCT. OCT devices are not interchangeable with regard to detection of macular structural progression.

Author(s): Mohammadzadeh, Vahid; Su, Erica; Heydar Zadeh, Sepideh; Law, Simon K; Coleman, Anne L; Caprioli, Joseph; Weiss, Robert E; Nouri-Mahdavi, Kouros | Abstract: PurposeDevelop a hierarchical longitudinal regression model for estimating local rates of change of macular ganglion cell complex (GCC) measurements with optical coherence tomography (OCT).MethodsWe enrolled 112 eyes with four or more macular OCT images and ≥2 years of follow-up. GCC thickness measurements within central 6 × 6 superpixels were extracted from macular volume scans. We fit data from each superpixel separately with several hierarchical Bayesian random-effects models. Models were compared with the Watanabe-Akaike information criterion. For our preferred model, we estimated population and individual slopes and intercepts (baseline thickness) and their correlation.ResultsMean (SD) follow-up time and median (interquartile range) baseline 24-2 visual field mean deviation were 3.6 (0.4) years and -6.8 (-12.2 to -4.3) dB, respectively. The random intercepts and slopes model with random residual variance was the preferred model. While more individual and population negative slopes were observed in the paracentral and papillomacular superpixels, superpixels in the superotemporal and inferior regions displayed the highest correlation between baseline thickness and rates of change (r = -0.43 to -0.50 for the top five correlations).ConclusionsA Bayesian linear hierarchical model with random intercepts/slopes and random variances is an optimal initial model for estimating GCC slopes at population and individual levels. This novel model is an efficient method for estimating macular rates of change and probability of glaucoma progression locally.Translational relevanceThe proposed Bayesian hierarchical model can be applied to various macular outcomes from different OCT devices and to superpixels of variable sizes to estimate local rates of change and progression probability.

PurposeTo compare local ganglion cell-inner plexiform layer (GCIPL) thickness measurements between 2 OCT devices and to explore factors that may influence the difference in measurements.DesignCross-sectional study.ParticipantsSixty-nine glaucoma eyes (63 patients) with evidence of central damage or mean deviation (MD) of -6.0 dB or worse on a 24-2 visual field (VF).MethodsCirrus and Spectralis OCT macular volume scans were exported, data from the central 20° of both OCT devices were centered and aligned, and 50× 50 arrays of 0.4°× 0.4° superpixels were created. We estimated nonparametric (Spearman's) correlations and used Bland-Altman plots to compare GCIPL thickness measurements between the two OCTs at the superpixel level. Factors that may have influenced the differences between thickness measurements between the two devices were explored with linear mixed models.Main outcome measuresPooled and individual-eye Spearman's correlation and agreement between thickness measurements from the two devices.ResultsThe median 24-2 VF MD was -6.8 dB (interquartile range [IQR], -4.9 to -12.3 dB). The overall pooled Spearman's correlation between the two devices for all superpixels and eyes was 0.97 (P < 0.001). The median within-eye correlation coefficient was 0.72 (IQR, 0.59-0.79). Bland-Altman plots demonstrated a systematic bias in most individual eyes, with Spectralis GCIPL measurements becoming larger than Cirrus measurements with increasing superpixel thickness. The average superpixel thickness and distance to the fovea influenced the thickness difference between the two devices in multivariate models (P < 0.001).ConclusionsLocal macular thickness measurements from the Spectralis and Cirrus devices are highly correlated, but not interchangeable. Differences in thickness measurements between the two devices are influenced by the location of superpixels and their thickness.