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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.

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.

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.

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.

PurposeTo test the hypothesis that visual field (VF) progression can be predicted from baseline and longitudinal optical coherence tomography (OCT) structural measurements.DesignProspective cohort study.MethodsA total of 104 eyes (104 patients) with ≥3 years of follow-up and ≥5 VF examinations were enrolled. We defined VF progression based on pointwise linear regression on 24-2 VF (≥3 locations with slope less than or equal to -1.0 dB/year and P < .01). We used elastic net logistic regression (ENR) and machine learning to predict VF progression with demographics, baseline circumpapillary retinal nerve fiber layer (RNFL), macular ganglion cell/inner plexiform layer (GCIPL) thickness, and RNFL and GCIPL change rates at central 24 superpixels and 3 eccentricities, 3.4°, 5.5°, and 6.8°, from fovea and hemimaculas. Areas-under-ROC curves (AUC) were used to compare models.ResultsAverage ± SD follow-up and VF examinations were 4.5 ± 0.9 years and 8.7 ± 1.6, respectively. VF progression was detected in 23 eyes (22%). ENR selected rates of change of superotemporal RNFL sector and GCIPL change rates in 5 central superpixels and at 3.4°and 5.6° eccentricities as the best predictor subset (AUC=0.79 ± 0.12). Best machine learning predictors consisted of baseline superior hemimacular GCIPL thickness and GCIPL change rates at 3.4° eccentricity and 3 central superpixels (AUC=0.81 ± 0.10). Models using GCIPL-only structural variables performed better than RNFL-only models.ConclusionsVF progression can be predicted with clinically relevant accuracy from baseline and longitudinal structural data. Further refinement of proposed models would assist clinicians with timely prediction of functional glaucoma progression and clinical decision making.

Purpose/aimThe optic nerve (ON) becomes taut during adduction beyond ~26° in healthy people and patients with primary open angle glaucoma (POAG), but only retracts the globe in POAG. We used magnetic resonance imaging (MRI) to investigate this difference.Materials and methodsMRI was obtained in 2-mm quasi-coronal planes in central gaze, and smaller (~23-25°) and larger (~30-31°) adduction and abduction in 21 controls and 12 POAG subjects whose intraocular pressure never exceeded 21mmHg. ON cross-sections were analyzed from the globe to 10 mm posteriorly. Area centroids were used to calculate ON path lengths and changes in cross-sections to calculate elongation assuming volume conservation.ResultsFor both groups, ON path was nearly straight (

Purpose To use optical coherence tomography (OCT) to 3-dimensionally characterize the optic nerve head (ONH) in peripapillary scleral bowing in non-highly myopic healthy eyes. Design Cross-sectional, multicenter study. Methods A total of 362 non-highly myopic (+6 diopters [D] > spherical equivalent > −6D) eyes of 362 healthy subjects from 20-90 years old underwent OCT ONH radial B-scan imaging. Bruch's membrane (BM), BM opening (BMO), anterior scleral canal opening (ASCO), and the peripapillary scleral surface were segmented. BMO and ASCO planes were fit, and their centroids, major axes, ovality, areas and offsets were determined. Peripapillary scleral bowing was characterized by 2 parameters: peripapillary scleral slope (ppSS) of 3 anterior peripapillary scleral segments (0-300, 300-700, and 700-1,000 μm from the ASCO centroid); and ASCO depth relative to a peripapillary scleral reference plane (ASCOD-ppScleral). Peripapillary choroidal thickness (ppCT) was calculated relative to the ASCO as the minimum distance between the anterior scleral surface and BM. Results Both ppSS and ASCOD-ppScleral ranged from slightly inward through profoundly outward in direction. Both parameters increased with age and were independently associated with decreased ppCT. Conclusions In non-highly myopic healthy eyes, outward peripapillary scleral bowing achieved substantial levels, was markedly increased with age, and was independently associated with decreased peripapillary choroidal thickness. These findings provide a normative foundation for characterizing this anatomy in cases of high myopia and glaucoma and in eyes with optic disc tilt, torsion, and peripapillary atrophy.

Author(s): Chen, Jessica Y; Le, Alan; Caprioli, Joseph; Giaconi, JoAnn A; Nouri-Mahdavi, Kouros; Law, Simon K; Bonelli, Laura; Coleman, Anne L; Demer, Joseph L | Abstract: PurposeTopical prostaglandin analogs (PGAs) are common treatment for primary open-angle glaucoma (POAG) but reportedly may cause adnexal fat atrophy. We asked if patients with POAG treated with PGAs have abnormalities in orbital fat volume (OFV).MethodsWe studied 23 subjects with POAG who had never experienced intraocular pressure (IOP) exceeding 21 mm Hg and were treated long term with PGAs, in comparison with 21 age-matched controls. Orbital volume, non-fat orbital tissue volume, and OFV were measured using high-resolution magnetic resonance imaging.ResultsSubjects with POAG had been treated with PGAs for 39 ± 19 months (SD) and were all treated within the 4 months preceding study. In the region from trochlea to orbital apex, OFV in POAG was significantly less at 9.8 ± 1.9 mL than in the control subjects at 11.1 ± 1.3 mL (P = 0.019). However, between the globe-optic nerve junction (GONJ) and trochlea, OFV was similar in both groups. Width and cross sectional area of the bony orbit were significantly smaller in POAG than in controls (P l 0.0001). Posterior to the GONJ, the average orbital cross-sectional area was 68.2 mm2 smaller, and the orbital width averaged 1.5 mm smaller throughout the orbit, in patients with POAG than in controls.ConclusionsPatients with POAG who have been treated with PGAs have lower overall OFV than controls, but OFV in the anterior orbit is similar in both groups. Lower overall OFV in POAG may be a primary association of this disorder with a horizontally narrower bony orbit, which may be a risk factor for POAG at nonelevated IOPs.

The purpose of this study was to evaluate the long-term outcomes of Descemet membrane endothelial keratoplasty (DMEK) in eyes that had previously undergone trabeculectomy and/or drainage device implantation.Retrospective, noncomparative case series.Medical records of 251 consecutive DMEK procedures performed by 1 surgeon (S.X.D.) from 2013 to 2017 were reviewed. Patients with ≥2 years of follow-up were divided into 3 groups: eyes with prior glaucoma surgery (ST), eyes with medically treated glaucoma (MT), and eyes without glaucoma (NG). Main outcomes measured were visual acuity, endothelial cell count (ECC), rates of secondary graft failure (SGF), and postoperative complications.Ninety procedures (87 eyes) met inclusion criteria. The mean follow-up period of all eyes was 38.4 ± 11.2 months (range, 24.2-64.4 months). At last follow-up, the proportion of eyes reaching a vision of ≥20/40 was higher than that before the DMEK procedure in each group (all P.05). The rate of ECC loss was the highest in the ST group compared to that in the MT and NG groups (63.8% vs 47.6% vs 44.0%, respectively; P.05) as well as the rate of SGF (41.6% vs 0% vs 2.4%, respectively; P.05). The rate of SGF of repeat DMEK was higher than that of primary DMEK (P.05). The rates of postoperative complications were similar among all groups (all P.05).In eyes with prior glaucoma surgery, DMEK achieved good long-term visual outcomes but experienced a higher rate of SGF than eyes without such comorbidity.

Purpose/Aim: We used magnetic resonance imaging (MRI) to investigate effects of intraocular pressure (IOP), race, and other factors on optic nerve (ON) traction in adduction, a phenomenon proposed as neuropathic in open angle glaucoma (OAG).Materials and Methods: Thirty-five patients with OAG (26 with maximal untreated IOP ≤21 mmHg, 9 with IOP >21mmHg) and 48 controls underwent axial and quasi-coronal MRI in central gaze and large (27-33°) abduction and adduction. Some underwent MRI at smaller ductions (21-28°). Effects of presence vs. absence of OAG; within OAG whether maximum IOP level was ≤21 mmHg vs. >21 mmHg; adduction angle; race; age; and gender on ON path length and globe translation were analyzed using generalized estimating equations to account for possible intereye correlations of individual subjects.Results: Average visual field mean deviation (±standard error of mean, SEM) was -8.2±1.2 dB in OAG with normal IOP, and -6.1±1.4 in high IOP. In central gaze, ON path in OAG was significantly more redundant than in controls but in both groups the ON became significantly and almost equally straighter in small (~21°) or large (~27°) adduction than in central gaze. With progressive adduction only, globes retracted in OAG (P

With the advent of spectral-domain optical coherence tomography, imaging of the posterior segment of the eye can be carried out rapidly at multiple anatomical locations, including the optic nerve head, circumpapillary retinal nerve fiber layer, and macula. There is now ample evidence to support the role of spectral-domain optical coherence tomography imaging of the macula for detection of early glaucoma. Macular spectral-domain optical coherence tomography measurements demonstrate high reproducibility, and evidence on its utility for detection of glaucoma progression is accumulating. We present a comprehensive review of macular spectral-domain optical coherence tomography imaging emerging as an essential diagnostic tool in glaucoma.

PurposeTo determine the frequency with which retinal tissues other than the nerve fibre layer, hereafter referred to as protruded retinal layers (PRL), are a component of optical coherence tomography (OCT) neuroretinal rim measurements.MethodsNinety healthy (30 White, Black and Japanese, respectively) subjects were included in the study. A radial scan pattern (24 B-scans centred on Bruch's membrane opening [BMO]) was used. For each of the 48 minimum rim width (MRW) measurement points, we determined whether PRL were present, absent or indeterminate. When present, the proportion of PRL within the MRW was quantified.ResultsProtruded retinal layers were present in 503 (11.6%), absent in 3805 (88.1%) and indeterminate in 12 (0.3%) measurement points. Overall, 69 (76.6%) subjects had ≥1 points with PRL, with White subjects having the highest frequency and Japanese the lowest (29 [97%] and 18 [60%], respectively; p&nbsp

Aim: We report patient safety and intraocular pressure (IOP) control after placement of a glaucoma drainage device (GDD) in eyes with a history of treated malignant uveal melanoma. Methods: A retrospective review of the records of patients with uveal melanoma was performed. Outcomes were local tumor recurrence, rate of metastases, and to­nometric success, based on survival curves, defined as IOP < 21 mm Hg. Results: Eleven eyes with choroidal melanoma, 4 with iris melanoma, and 1 with ciliary body melanoma were followed for a median (interquartile range) of 2.1 (1.1–3.2) years. Two subjects developed liver metastases; one had monosomy 3 and tumor gene expression profile class 2. The other case with ciliary body melanoma was negative for monosomy 3. There were no cases of local treatment failure. Mean preoperative IOP decreased from 30.5 ± 7.7 to 15.9 ± 8.1 mm Hg at 1 year after surgery (1-year success rate 80%). Conclusions: Our case series with a median follow-up of 2 years shows that placing a GDD in patients with treated uveal melanoma does not expose patients to greater risk of local or extraocular recurrence. A larger series and longer follow-up time are required to fully evaluate the safety of GDDs in this clinical scenario.

Celastrol, a quinine methide triterpene extracted from the perennial vine Tripterygium wilfordii, has been identified as a neuroprotective agent in various models of neurodegenerative disorders. We have reported earlier that systemic and intravitreal administration of celastrol stimulate the survival of retinal ganglion cells (RGCs) injured by optic nerve crush (ONC) and that mechanisms underlying celastrol׳s RGC protection may be associated with inhibition of TNF-alpha-mediated cell death. The present study evaluates the effect of celastrol on the survival of RGCs injured by ocular hypertension. Intraocular pressure (IOP) elevation resulted in approximately 23% of RGCs loss. Reduction in RGC numbers was observed in all four retinal quadrants: 30% in superior, 17% in inferior, 11% in nasal and 35% in temporal regions. Celastrol (1 mg/kg) or vehicle (DMSO) was administered three times per week by intraperitoneal injection, starting on the day of laser photocoagulation of the TM and continued for the entire duration of the experiment (5 weeks). Celastrol treatment stimulated RGC survival by an average of 24% in the entire retina compared to the vehicle-treated group. RGC numbers were increased in all four quadrants: approximately 40%, 17%, 15% and 30% more RGCs were counted in the superior, inferior, nasal and temporal regions, respectively. The average RGC numbers for the entire retinas of the celastrol/IOP group were only ∼5% and 10% lower than that in vehicle- or celastrol-injected animals with normal IOP, respectively. Our data indicate a significant celastrol-mediated neuroprotection against elevated IOP-induced injury.

PURPOSE To evaluate outcomes of trabeculectomy with adjunctive mitomycin C in patients with uncontrolled intraocular pressure (IOP) after glaucoma drainage device implantation. MATERIALS AND METHODS Consecutive patients who had undergone a trabeculectomy after GDD were reviewed. The primary outcome was surgical success with stratified IOP targets based on the following criteria: (A) IOP

Purpose To describe a case of macular microcysts associated with advanced secondary glaucoma from Schwartz-Matsuo syndrome. Methods Clinical presentation, color fundus photography, optic disk photography, visual fields, and optical coherence tomography are presented. Results A 32-year-old woman presented with advanced, unilateral secondary glaucoma associated with a macula-on rhegmatogenous retinal detachment. She was diagnosed with Schwartz-Matsuo syndrome. Spectral domain optical coherence tomography showed macular microcystic changes in the paracentral retina at the level of the inner nuclear layer. Conclusion Macular microcystic changes in the paracentral inner nuclear layer on spectral domain optical coherence tomography have been described in eyes with optic atrophy associated with a variety of diseases. This is the first described case of macular microcysts associated with advanced secondary glaucoma from Schwartz-Matsuo syndrome and may offer insights into the pathogenesis of these microcysts.

Elevated intraocular pressure (IOP) is a major risk factor for the development and progression of glaucoma. Previous prospective, randomized, long-term studies have demonstrated the strength of IOP reduction in slowing the progression of disease. It is well known that IOP is not a fixed value but fluctuates considerably over time. Although there have been some studies on IOP fluctuation and the progression of glaucoma, whether IOP fluctuation is an independent risk factor for glaucomatous damage and disease progression remains controversial. In this article, we reviewed the definition of IOP fluctuation, and both the evidence and the speculation for and against the effect of IOP fluctuation on glaucoma progression. Although conclusions seem to vary from study to study, we considered that different studies examined different groups of patients, at different stages of disease, and at different IOP levels. Our conclusion is that these apparently disparate results are not conflicting, but rather can be viewed as complementary. In clinical care, we recommend the consideration of IOP “modulation” rather than just IOP “reduction” when glaucoma patients are treated. Quality-based IOP control may be more effective than quantity-based IOP reduction to prevent or retard disease progression.

Purpose To investigate differences across the visual field (VF) in the rate of glaucomatous progression, the likelihood of defect in four disease severity cross-sections, and comparisons of subgroups in each of between 12 demographic, comorbid, and clinical variables. Methods Two long-term glaucoma clinical trials used Humphrey Field Analyzer 24-2 VFs to calculate pointwise deviations from age-matched normal controls. Slopes of glaucomatous progression over time were calculated per participant using linear mixed models. Pointwise differences between subgroups in slopes and cross-sectional categories were tested, adjusting for multiple comparisons using false discovery rate (FDR) and Q values. Results Pointwise data were available for 1118 patients who had 15,073 VFs. On average, defects were seen at all VF points. Of the 12 variables, six had average pointwise slopes where Subgroup 1 had significantly faster progression than Subgroup 2 at all or many of the 52 VF points: participants who were older (≥65 vs. younger), 52/52; were male, 13/52; had diabetes, 29/52; had hypertension, 46/52; had a larger cup-to-disc ratio (≥0.7), 36/52; or had larger differences in absolute mean deviation (MD) between eyes (>3 dB), 52/52. Cross-sectional patterns at MD severity of -12 to -6.1 dB showed strong midline effects for gender and other patterns for hypertension, cup-to-disc ratio, absolute difference in MD between eyes, and disc notching. Conclusions The approach used provides new longitudinal and cross-sectional insights into variation across the VF associated with demographic, comorbid, and clinical variables. Translational relevance This exploration and characterization of variable effects in the setting of pointwise VF testing may enable clinicians to anticipate patterns of VF loss based on demographic, comorbid, and clinical associations.

Purpose To examine risk factors for low intraocular pressure (IOP) after trabeculectomy and to describe long-term outcomes in these eyes. Design Retrospective case-control study. Participants Cases with low IOP included all patients with IOP ≤5 mmHg on 3 or more consecutive visits 3 months or later after trabeculectomy. Control patients without low IOP after trabeculectomy were randomly selected at a 1:2 case-to-control ratio. Methods A case-control study was performed of patients undergoing trabeculectomy at the Stein Eye Institute. Covariates included demographics, history of cataract surgery, refractive error, number of glaucoma medications, family history of glaucoma, diabetes, hypertension, visual acuity (VA), IOP, number of sutures in the scleral flap, laser suture lysis, surgeon, and laterality of surgery. Logistic regression modeling was used to examine associations between each covariate and low IOP. Postoperative outcomes that were examined included reoperation, vision loss, and surgical failure. The time between trabeculectomy and each outcome was compared between cases and controls with Cox proportional hazards regression modeling. Main Outcome Measures Low IOP after trabeculectomy, reoperation, vision loss, and surgical failure. Results Of 3659 total trabeculectomies performed by 5 surgeons between 1990 and 2013, 64 eyes had low IOP (1.7%), which were compared with 130 control eyes. Fifteen of the 64 eyes with low IOP had hypotony maculopathy (23.4%). After accounting for differences in baseline IOP, laser suture lysis was negatively correlated with low IOP after trabeculectomy (odds ratio [OR], 0.33; 95% confidence interval [CI], 0.13–0.87); surgeon was correlated with high vs. low IOP after trabeculectomy (OR, 5.32; 95% CI, 1.53–18.52). There were no statistically significant associations between low IOP and time to reoperation (hazard ratio [HR], 0.73; 95% CI, 0.32–1.68), vision loss (HR, 1.77; 95% CI, 0.81–3.88) or surgical failure (HR, 1.14; 95% CI, 0.62–2.11). In patients with low IOP, there was a higher unadjusted incidence of bleb revision in patients who had maculopathy (7.6 vs. 1.9 revisions/100 person-years; for maculopathy versus no maculopathy P = 0.008). Conclusions The absence of laser suture lysis and surgeon are factors potentially associated with low IOP after trabeculectomy. Numeric hypotony does not necessarily represent clinical failure after trabeculectomy.

To explore the correlation of local macular ganglion cell/inner plexiform layer (GC/IPL) thickness measurements with sensitivity at individual test locations on the central 10-2 visual fields (VFs) in patients with glaucoma.One hundred thirty-seven eyes of 125 patients with spectral domain optical coherence tomography (OCT) and 10-2 VFs were included. The exported thickness matrices (200×200) of GC/IPL measurements were centred on the fovea. Total deviation values at each test location were correlated with the 20 000 GC/IPL thickness measurements in the corresponding inferior or superior hemiretina, and areas of highest correlation were plotted. Macular structure-function relationships were also examined between six wedge-shaped GC/IPL sectors and the corresponding VF clusters. A multivariate model was built to identify the 10-2 VF test locations associated with each GC/IPL sector thickness.Average mean deviation on 10-2 VFs was -9.2±6.1 dB. The 10-2 VF test points demonstrated correlations with GC/IPL thickness in localised arcuate patterns mostly limited within the central 4.8×4.0 mm measurement ellipse (ρ=0.43-0.74, p0.05 for all). Twenty-one test points of the 10-2 VF were the best predictors of sectoral GC/IPL thickness. Sectoral VF-OCT correlations were high (ρ=0.53-0.66, p0.001) and did not significantly change after adjusting for retinal GC displacement (p0.05).Macular OCT/VF relationships have localised arcuate characteristics in the central region of the macula. Given the overlapping nature of structure-function relationships, a smaller number of VF test locations may be used to summarise macular functional damage.NCT01742819.

Purpose To test the hypotheses that: (1) structure–function (SF) relationships between visual fields (VF) and Bruch's membrane opening-based minimum rim width (BMO-MRW) measurements are superior to those for peripapillary retinal nerve fiber layer (pRNFL) in perimetric glaucoma; (2) BMO-MRW measurements may extend the utility of structural measurement across the range of glaucoma severity; and (3) to estimate the influence of Bruch's membrane opening (BMO) size on BMO-MRW measurements. Methods One hundred eight perimetric glaucoma eyes (68 patients) with good quality spectral-domain optical coherence tomography images of the optic disc and pRNFL, and reliable VF within 6 months were recruited. Relationship of global and sectoral BMO-MRW and pRNFL thickness with corresponding VF parameters and the influence of normalizing BMO-MRW (on BMO circumference, nBMO-MRW) on SF relationships were investigated. Broken-stick models were used to compare the point at which pRNFL and BMO-MRW parameters reached their measurement floor. Results The median (interquartile range) of VF mean deviation was −5.9 (−12.6 to −3.6) dB. Spearman correlation coefficients between pRNFL, BMO-MRW, and nBMO-MRW measures and corresponding VF cluster average deviations ranged between 0.55 to 0.80, 0.35 to 0.66, and 0.38 to 0.65, respectively. Bruch's membrane opening–MRW parameters demonstrated weaker SF relationships compared with pRNFL globally and in temporal, temporal-superior, and nasal-inferior sectors (P < 0.03). Normalization of BMO-MRW did not significantly influence SF relationships. Conclusions Structure–function relationships were somewhat weaker with BMO-MRW parameters compared with pRNFL in eyes with perimetric glaucoma. Bruch's membrane opening–MRW normalization did not significantly change SF relationships in this group of eyes with mild departures from average BMO size.

Purpose The purpose of this study was to compare rates of change of various macular thickness measures and evaluate the influence of baseline damage on macular rates of change. Methods One hundred twelve eyes (112 patients) with ≥ 2 years of follow-up and ≥ 5 macular optical coherence tomography (OCT) images and 10-2 visual field (VF) tests were included. OCT measures of interests were full macular thickness (FMT), ganglion cell complex (GCC), ganglion cell/inner plexiform layer (GCIPL), ganglion cell layer (GCL), and outer retinal layer (ORL) thickness in 3° × 3° superpixels. Rates of change were estimated with linear regression and normalized by dividing rates by the average normative superpixel thickness. We compared rates of change and proportion of significantly worsening superpixels (detection rate) and improving superpixels (false discovery rate [FDR]) among macular measures as a function of baseline thickness and 10-2 VF status. Results Median (interquartile range [IQR]) baseline VF mean deviation, follow-up time, and number of VFs/OCTs were -7.6 dB (-11.8 to -3.8 dB), 4.5 years (4.0-5.0 years), and 9 (8-10), respectively. Normalized FMT and GCC rates of change were faster and detection rates were higher than GCIPL and GCL (P < 0.001), but FMT had lower FDR than GCC (P = 0.02); faster FMT rates were partially explained by ORL rates of change. GCC detection rates were less likely than GCIPL and GCL rates to decrease with diminishing baseline thickness or worse VF damage. In eyes with 10-2 VF worsening, GCC and GCL demonstrated the fastest rates of change. Conclusions GCC measurements are most likely to detect structural worsening along the spectrum of glaucoma severity. Although FMT rates of change are least influenced by baseline thickness, they partially reflect likely age-related ORL changes. Translational Relevance GCC thickness measurements seem to be the optimal macular outcome measure for detection of glaucoma deterioration.

Purpose To evaluate outcomes of an ab externo surgical technique combining cyclopexy with partial-thickness scleral flap dissection and suture reattachment of ciliary muscle and cryopexy through partial-scleral bed for cyclodialysis cleft repair. Materials and methods Consecutive patients in a tertiary academic practice with cyclodialysis cleft confirmed by gonioscopy or ultrasound biomicroscopy and had received the combined procedure were reviewed. Primary outcomes included differences between the preoperative and postoperative best-corrected visual acuity (BCVA) and intraocular pressure (IOP). Secondary outcomes included complications and additional surgeries. Results Six consecutive patients (eyes) from October 2006 to November 2012 (6 y) were enrolled. No patient had received prior laser or surgical treatment for cyclodialysis cleft. Patient's age ranged from 14 to 81 years (median=37 y). Follow-up ranged from 1 to 72 months (median=12 mo). The cyclodialysis clefts of 3 patients (50%) were caused by blunt injuries and the other 3 (50%) from complicated intraocular surgery. Preoperative BCVA ranged from 20/40 to counting fingers with mean IOP of 2.3±2.1 mm Hg (range, 0 to 6 mm Hg). Final postoperative BCVA ranged from 20/20 to hand motions with mean IOP of 11.3±5.7 mm Hg (range, 3 to 18 mm Hg). Five patients (83%) had an increase in IOP and recovery of vision to 20/50 or better at the final visit (including further surgeries). No complication was noted and no additional cyclopexy was required. Conclusions Combined ab externo cyclopexy with partial-thickness scleral flap dissection and suture reattachment of the ciliary muscle and cryopexy delivered on the partial-thickness scleral bed is safe and effective as primary surgical repair for cyclodialysis cleft.

Author(s): Yang, Hongli; Luo, Haomin; Gardiner, Stuart K; Hardin, Christy; Sharpe, Glen P; Caprioli, Joseph; Demirel, Shaban; Girkin, Christopher A; Liebmann, Jeffrey M; Mardin, Christian Y; Quigley, Harry A; Scheuerle, Alexander F; Fortune, Brad; Chauhan, Balwantray C; Burgoyne, Claude F | Abstract: Purpose:To quantify peripapillary choroidal thickness (PCT) and the factors that influence it in healthy participants who represent the racial and ethnic composition of the U.S. population. Methods:A total of 362 healthy participants underwent optical coherence tomography (OCT) enhanced depth imaging of the optic nerve head with a 24 radial B-scan pattern aligned to the fovea to Bruch's membrane opening axis. Bruch's membrane, anterior scleral canal opening (ASCO), and the anterior scleral surface were manually segmented. PCT was measured at 100, 300, 500, 700, 900, and 1100 μm from the ASCO globally and within 12 clock-hour sectors. The effects of age, axial length, intraocular pressure, ethnicity, sex, sector, and ASCO area on PCT were assessed by ANOVA and univariable and multivariable regressions. Results:Globally, PCT was thicker further from the ASCO border and thinner with older age, longer axial length, larger ASCO area, European descent, and female sex. Among these effectors, age and axial length explained the greatest proportion of variance. The rate of age-related decline increased further from the ASCO border. Sectorally, the inferior-temporal sectors were thinnest (10.7%-20.0% thinner than the thickest sector) and demonstrated a higher rate of age-related loss (from 15.6% to 20.7% faster) at each ASCO distance. Conclusions:In healthy eyes, PCT was thinnest in the inferior temporal sectors and thinner PCT was associated with older age, European descent, longer axial length, larger ASCO area, and female sex. Among these associations, age had the strongest influence, and its effect was greatest within the inferior temporal sectors.

To identify baseline and longitudinal risk factors for fast visual field (VF) decay in patients with open-angle glaucoma.Retrospective cohort study.Patients with open-angle glaucoma with ≥6 VFs and ≥4 years of follow-up were included. VF decay rates were measured with the following methods: mean deviation (MD) rate, VF index (VFI) rate, and the Glaucoma Rate Index (GRI). The relationship between VF rates and clinical variables were investigated with linear mixed models. Logistic regression analysis was performed to determine which factors were associated with fast progression.A total of 1317 eyes of 745 patients with a mean (± SD) age of 63.3 (±10.9) years and a median (interquartile range) MD -2.4 (-0.7 to -5.6) dB at baseline were analyzed. The median (interquartile range) number of VFs was 12 (9 to 16), and mean follow-up duration was 11.5 (±3.7) years. Older age (P.001), higher peak intraocular pressure (IOP) (P.001), and glaucoma surgery during the study period (P.001) were associated with faster rates of progression regardless of the method used. Worse baseline MD was associated with MD rate (P = .02), but neither with VFI rate (P = .37) nor GRI (P = .31); whereas pseudoexfoliative glaucoma was associated with faster rates of progression with MD (P = .008) and VFI (P = .01) rates, but not with GRI. Higher peak IOPs (P = .005) was a significant predictor for fast progression.In this cohort, older age, peak IOP, pseudoexfoliative glaucoma, and baseline MD were associated with the rate of glaucomatous VF worsening. Fast progressors had a higher peak IOP than non-fast progressors. The identification and appropriately aggressive treatment of fast progressors would reduce visual disability from glaucoma.

To evaluate long-term tonometric outcomes of same-site trabeculectomy revision with mitomycin C (MMC) after failure of an initial trabeculectomy, and to identify risk factors for failure in patients with open-angle glaucoma.Retrospective cohort study.One-hundred and seventeen patients (130 eyes) with primary open-angle, pseudoexfoliation, or pigmentary glaucoma, who failed a first trabeculectomy and who were ≥40 years of age at the time of same-site trabeculectomy revision, were included. Three levels of success criteria were defined: (A) intraocular pressure (IOP) ≤18 mm Hg and IOP reduction of 20%; (B) IOP ≤15 mm Hg and IOP reduction of 25%; and (C) IOP ≤12 mm Hg and IOP reduction of 30%. The primary outcome was the qualified Kaplan-Meier success rate (with or without medications) for each criterion. Cox multivariate regression analysis was used to identify risk factors for failure.The success rates (± standard error) at the first, third, and fifth years of follow-up for criterion A were 69.7% (± 4.1%), 58.2% (± 4.6%), and 51.1% (± 5.0%); for criterion B these were 60.9% (± 4.4%), 47.8% (± 4.7%), and 44.0 (± 4.8%); and for criterion C, 44.6% (± 4.5%), 29.7% (± 4.4%), and 25.8% (± 4.3%). Mean follow-up was 5.2 (± 3.6) years. A time interval between the first and the same-site trabeculectomy revision of3 years, worse baseline visual acuity, and dyslipidemia were significant risk factors for failure.Given the long-term tonometric success rates along with significant medication reduction, same-site trabeculectomy revision with MMC should be considered as a viable option to achieve reasonable IOP targets after a first failed trabeculectomy in open-angle glaucoma patients.

To measure the magnitude and direction of visual field (VF) rates of change in glaucoma patients after intraocular pressure (IOP) reduction with trabeculectomy.Retrospective, comparative, longitudinal cohort study.Patients with open-angle glaucoma.Patients who underwent trabeculectomy (Trab) with mitomycin-C (74 eyes of 64 patients) with ≥4 reliable VF measurements before and after trabeculectomy and at least 4 years of follow-up before and after surgery were included. Decay or improvement exponential models were used to calculate pointwise rates of perimetric change before and after surgery. A separate comparison (Comp) group with unoperated glaucoma (71 eyes of 65 patients) with similar baseline damage, number of VF tests, and follow-up was used to address possible regression to the mean. Proportions of VF locations decaying or improving before and after surgery in the Trab group, and during the first and second halves of follow-up in the Comp group, were calculated. A multivariate analysis was used to explore variables associated with VF improvement.The rate of pointwise VF change before and after surgery in the Trab group and Comp group.Patients in the Trab group were followed for 5.1±2.1 years (mean ± standard deviation) before and 5.4±2.3 years after surgery, with 8.9±4.7 VF tests before and 9.0±4.4 VF tests after surgery. The mean rate of change for all VF locations slowed from -2.5±9.3%/year before surgery to -0.10±13.1%/year after surgery (P0.001). In the Trab group, 70% of locations decayed and 30% improved preoperatively; postoperatively, 56% decayed and 44% improved. The differences between the Trab and Comp groups were significant (P0.0001, chi-square test). The magnitude of IOP reduction correlated with the excess number of VF locations that exhibited long-term improvement postoperatively (P = 0.009). In the Trab group, 57% of eyes had ≥10 improving VF locations postoperatively.The results show that trabeculectomy slows the rate of perimetric decay and provide evidence of sustained, long-term improvement of visual function in glaucoma. These findings suggest the possibility of reversal of glaucomatous dysfunction of retinal ganglion cells and their central projections.

PURPOSE To compare the accuracy of the "ISNT" rule [neural rim width of inferior(I)≥superior(S)≥nasal(N)≥temporal(T) regions] and the abbreviated variant, the "IS" rule (inferior≥superior regions) to differentiate normal from glaucomatous eyes. MATERIALS AND METHODS Medical records of patients who were evaluated in 2011, had glaucomatous optic neuropathy and visual field defects, on glaucoma treatment, and had stereoscopic optic disc photographs were reviewed. Optic discs with focal complete loss of neural rim or long axis rotated >30 degrees from vertical meridian, and patients with ≥5 D of myopia or any retinal pathology or nonglaucomatous optic neuropathy were excluded. One eye per patient was randomly enrolled. Normal control eyes were also included. Rim widths were measured with an image processing program (ImageJ, National Institutes of Health) in a masked manner. The sensitivity and specificity of the ISNT rule, the IS rule, and cup-to-disc ratio (CDR) were compared. RESULTS A total of 134 glaucoma and 110 normal eyes were enrolled. The mean CDRs of the glaucoma and normal eyes were 0.65±0.13 and 0.39±0.15, respectively. Sensitivities of the ISNT and IS rules were 85% and 41%, respectively, whereas specificities were 46% and 85%, respectively. Application of the IS rule in eyes with larger CDR (>0.57) increased the specificity of the IS rule to 93% while keeping the sensitivity at 41%. When ISNT or IS rule and CDR>0.57 were combined in differentiating normal from glaucomatous eyes for the entire sample, specificities approached 90% and 99%, respectively. CONCLUSIONS The ISNT rule alone has a high sensitivity but relatively low specificity. Application of the IS rule in eyes with increased CDR yields a much higher specificity for differentiating normal from more advanced glaucomatous eyes. A combination of different features of the optic disc (increase of CDR and ISNT or IS rule) improves the specificity of optic disc evaluation for glaucoma.

Author(s): Alizadeh, Reza; Vickers, Laura; Hirunpatravong, Pradtana; Romero, Pablo; Lin, Mark C; Sharifipour, Farideh; Caprioli, Joseph | Abstract: PurposePrimary open-angle glaucoma (POAG) patients constitute a heterogenous group. Identification of phenotypic subtypes among these patients may provide a deeper understanding of the disease and aid associations with genotypes. We describe a phenotype of POAG patients associated with a constellation of systemic disorders; patients with this phenotype seem to be vulnerable to optic nerve damage at low intraocular pressures.Materials and methodsIn this retrospective study, we evaluated the medical records of active Jules Stein Eye Institute glaucoma patients from January 1996 to 2017 and included subjects with POAG, acquired pits of the optic nerve (APON), and at least one of the following: systolic blood pressure persistently ≤100 mm Hg, history of migraine headaches or migraine variant, and the Raynaud syndrome.ResultsOf 87 patients (125 eyes) with APON, 37 patients (55 eyes) met the study criteria. In total, 34 patients were female (92%). The median age at the time of diagnosis was 55 years. Nineteen patients (73%) had low systolic blood pressures, same number had Raynaud syndrome, and 25 (68%) had a history of migraine.ConclusionsWe describe a POAG subtype with APON and systemic vascular instability, predominantly female in their sixth decade of life who demonstrate progressive glaucomatous visual field damage at low intraocular pressure. We suggest that this clinical picture represents an important phenotype of POAG, and that identification and further study of it will help guide diagnosis and development of individualized treatments.

Author(s): Moghimi, Sasan; Fatehi, Nima; Nguyen, Andrew H; Romero, Pablo; Caprioli, Joseph; Nouri-Mahdavi, Kouros | Abstract: Purpose:To explore factors influencing the inner plexiform layer (IPL) in healthy subjects and to test the hypothesis that IPL thickness is preferentially decreased in glaucoma as compared with ganglion cell layer (GCL) thickness. Methods:Ninety-nine glaucomatous eyes and 66 healthy eyes (165 subjects) underwent macular spectral-domain optical coherence tomography (SD-OCT) imaging and GCL and IPL were segmented creating 8 × 8 arrays of 3° × 3° superpixels. The central 24 superpixels were categorized into three levels of eccentricity (∼1.5°, 4.5°, and 7.5° from the foveal center). Linear mixed models were used to determine predictive parameters for IPL thickness in healthy subjects and to explore the influence of diagnosis of glaucoma on IPL thickness taking into account the effect of GCL thickness and other covariates. Results:Being located at 4.5° eccentricity predicted thicker IPL compared with 1.5° eccentricity (P l 0.001) in multivariable models in healthy subjects, whereas older age (P = 0.001) and Asian ethnicity (P = 0.021) were associated with thinner IPL. Diagnosis of glaucoma was not associated with thinner IPL regardless of eccentricity after accounting for age and ethnicity. The results were similar when only eyes with mean deviation greater than -6 dB were analyzed. Conclusions:Ethnicity and distance from the fovea are the main determinants of IPL thickness in the central macula. Preferential thinning of the macular IPL, compared with GCL, could not be detected in this study regardless of glaucoma stage. Translational Relevance:There is no evidence for preferential thinning of the macular IPL in glaucoma compared with GCL based on currently available SD-OCT-imaging technology.

Importance There is evidence that patients of African descent (AD) experience higher surgical failure rate after trabeculectomy without antimetabolites. Objective To compare outcomes of initial trabeculectomy with mitomycin C in AD patients with those of patients of European descent (ED) and to identify prognostic factors for failure. Design, Setting, and Participants In this retrospective matched cohort study, 135 eyes of 105 AD patients were matched with 135 eyes of 117 ED patients by age (within 5 years), surgeon, lens status, and follow-up time (within 1 year) from a single tertiary academic center. Interventions Initial trabeculectomy with mitomycin C. Main Outcomes and Measures Criteria A, B, and C defined qualified success rates as final intraocular pressure of 18 mm Hg or less, 15 mm Hg or less, and 12 mm Hg or less, respectively, in addition to 20% or more, 25% or more, and 30% or more reduction of intraocular pressure or reduction of 2 or more medications. Kaplan-Meier survival curves were compared with log-rank test in AD and ED patients, and Cox proportional hazard models were used to estimate the influence of race/ethnicity on surgical success accounting for confounding variables. Results Of the 105 AD patients, 56 (53.3%) were female, and the mean (SD) age was 67.5 (10.4) years; of the 117 ED patients, 64 (54.7%) were female, and the mean (SD) age was 68.2 (10.0) years. For AD patients compared with ED patients, the qualified success rates at 5 years for criteria A were 61% and 67%, respectively (difference, 7.3%; 95% CI, 4.4-10.4); for criteria B, 43% and 60% (difference, 17.6%; 95% CI, 15.2-20.0); and for criteria C, 25% and 40% (difference, 15.8%; 95% CI, 11.1-20.5). On multivariable Cox regression analyses, AD was associated with higher failure rate with criteria B and C for qualified success and with all criteria for complete success (ie, no need for medications). Incidence of bleb leaks was higher in the AD group (29 vs 11 eyes;P = .002). Additionally, AD patients required additional glaucoma surgeries more often than ED patients (47 vs 26 eyes;P = .004). Conclusions and Relevance African descent was associated with higher failure rates and higher incidence of bleb leaks after initial trabeculectomy with mitomycin C compared with European descent. If this is subsequently shown to be a cause and effect, the findings need to be considered when surgical treatment of glaucoma is contemplated in AD patients.

Purpose:To quantify the influence of ocular and demographic factors on central laminar depth (LD) in healthy participants. Methods:A total of 362 normal subjects underwent optical coherence tomography (OCT) enhanced depth imaging of the optic nerve head (ONH) with a 24 radial B-scan pattern aligned to the fovea-to-Bruch's membrane opening (BMO) axis. BMO, anterior lamina, anterior scleral canal opening (ASCO), Bruch's membrane (BM), and the peripapillary scleral surface were manually segmented. The extent of laminar segmentation was quantified within 72 ASCO subsectors. Central LD was quantified relative to four reference planes: BMO, ASCO, BM, and scleral. The effects of age, sex, ethnicity, IOP, BMO area, ASCO area, and axial length on LD were assessed. Results:Laminar visibility was most consistent within the central ASCO (median 89%, range, 69%-95%). LDBMO and LDBM were significantly shallower in eyes with greater age, BMO area, and axial length and in females. LDASCO was shallower in eyes with greater ASCO area and axial length and in European and Hispanic descent compared to African descent eyes. LDSclera behaved similarly, but was not associated with axial length. BMO and ASCO area were not different between African descent and European descent eyes. Conclusions:Central LD was deeper in African descent eyes and influenced least by age, axial length, and sex, but more by ASCO area, when measured relative to the ASCO and sclera. However, the magnitude of these effects for all four reference planes was small, and their clinical importance in the detection of glaucoma and its progression remains to be determined.

Programmed cell death-1 (PD-1) is a key negative receptor inducibly expressed on T cells, B cells and dendritic cells. It was discovered on T cells undergoing classical programmed cell death. Studies showed that PD-1 ligation promotes retinal ganglion cell (RGC) death during retinal development. The purpose of this present study is to characterize PD-1 regulation in the retina after optic nerve crush (ONC). C57BL/6 mice were subjected to ONC and RGC loss was monitored by immunolabelling with RNA-binding protein with multiple splicing (Rbpms). Time course of PD-1 mRNA expression was determined by real-time PCR. PD-1 expression was detected with anti-PD-1 antibody on whole mount retinas. PD-1 staining intensity was quantitated. Colocalization of PD-1 and cleaved-caspase-3 after ONC was analyzed. Real-time PCR results demonstrated that PD-1 gene expression was significantly upregulated at day 1, 3, 7, 10 and 14 after ONC. Immunofluorescent staining revealed a dramatic increase of PD-1 expression following ONC. In both control and injured retinas, PD-1 tended to be up-expressed in a subtype of RGCs, whose somata size were significantly larger than others. Compared to control, PD-1 intensity in large RGCs was increased by 82% in the injured retina. None of the large RGCs expressed cleaved-caspase-3 at day 5 after ONC. Our work presents the first evidence of PD-1 induction in RGCs after ONC. This observation supports further investigation into the role of PD-1 expression during RGC death or survival following injury.

The interest in minimally invasive glaucoma surgical (MIGS) procedures and devices stems from a desire to have a surgical option for the treatment of glaucoma that is associated with less serious risks and fewer complications than established procedures. Furthermore, a relatively simple and safe surgical approach may help to reduce side effects associated with medication use and to reduce the problem of poor adherence with medical therapy in glaucoma patients. The Food and Drug Administration (FDA) Center for Devices and Radiological Health has received many requests for investigational trials for novel glaucoma surgical devices. Still, there is no consensus regarding the appropriate populations in which to implant these devices, nor are there uniform views by ophthalmologists and researchers concerning the best methods for the assessment of their safety and effectiveness. The FDA and the American Glaucoma Society collaborated in hosting a public meeting on February 26, 2014, in Washington, DC, to discuss guidelines for the evaluation of the safety and effectiveness of MIGS devices. Glaucoma specialists from across the United States and Canada discussed the appropriate clinical trial populations and defined clear and reasonable outcomes for the evaluation of their safety and effectiveness.

Purpose To evaluate acupuncture as treatment for glaucoma. Design Prospective double-masked randomized crossover study. Methods setting: Clinical practice. population: One eye per patient with primary open-angle glaucoma and stable intraocular pressure (IOP). intervention: Patients were randomized to receive 1 acupuncture series (12 sessions with either eye-related [eye-points] or non-eye-related [non-eye-points] acupoints) and then crossed over to receive the other series. outcome measures: IOP, blood pressure (BP), heart rate (HR), best-corrected visual acuity (BCVA), visual field (VF), optic disc and peripapillary retinal nerve fiber layer (RNFL) measurements, compliance, and adverse reactions. Probability to detect 3 mm Hg IOP difference between series was 90%. Results Twenty-two patients volunteered and 11 (50.0%) completed the study; 8 (36.4%) did not complete treatment owing to changes of health, moving away, lack of transportation, or family crisis; and 3(13.6%) were withdrawn owing to needle sensitivity or IOP elevation (8 mm Hg) in the contralateral eye. After an acupuncture session, mean IOP increased slightly with both eye-points (from 12.9 ± 1.8 mm Hg to 13.6 ± 2.0 mm Hg, P = .019) and non-eye-points (from 13.0 ± 1.5 mm Hg to 13.5 ± 1.7 mm Hg, P = .073) series. HR, diurnal IOP, and BCVA showed no statistically significant changes after 12 sessions of either series. Systolic and diastolic BP were reduced after 12 sessions of non-eye-points series ( P = .040, P = .002, respectively). Optic disc, RNFL, and VF showed no statistically significant changes. Conclusions Acupuncture has no overall effect on diurnal IOP or BCVA but may temporally increase the IOP immediately after a treatment session. BP is lowered by acupuncture with non-eye-points, but not with eye-points. Compliance and adverse event rates were low.

Identifying whether an association exists between daily dietary polyunsaturated fatty acid (PUFA) consumption and the prevalence of glaucoma in the United States may provide modifiable dietary risk factors for the development of glaucoma.To analyze the association between glaucoma and daily dietary intake of PUFAs, including ω-3 fatty acids, in the US population.Data from 3865 participants in the National Health and Nutrition Examination Survey (NHANES) 2005-2008 database who were 40 years or older, had participated in the vision health and dietary intake questionnaires, and had available results from laboratory tests and eye examinations that included frequency-doubling technology visual field loss detection tests and optic disc photographs were included. Data collection was performed by NHANES from 2005 to 2006. Data for the present study were downloaded from their database May 1 to 30, 2017. Data analyses were performed from June 1 to October 1, 2017.Daily dietary intake of PUFAs, including ω-3 fatty acids.Prevalence of glaucoma in the United States as defined using the Rotterdam criteria, which included a combination of optic cupping or asymmetry and visual field defect results.Of the 83 643 392 weighted survey participants included in this cross-sectional study, 43 660 327 (52.2%) were women and 3 076 410 (3.7%) met our criteria for having glaucoma. Compared with participants without glaucoma, those with glaucoma were older (mean [SE] age, 61.4 [0.8] vs 53.7 [0.4] years; P .001). Increased levels of daily dietary intake of eicosapentaenoic acid (odds ratio [OR], 0.06; 95% CI, 0.00-0.73) and docosahexaenoic acid (OR, 0.06; 95% CI, 0.01-0.87) were associated with significantly lower odds of having glaucoma. However, participants with daily total dietary PUFA intake levels in the second (OR, 2.84; 95% CI, 1.39-5.79) and third (OR, 2.97; 95% CI, 1.08-8.15) quartiles showed significantly increased odds of meeting our criteria for a diagnosis of glaucoma.Increased daily dietary consumption levels of eicosapentaenoic acid and docosahexaenoic acid were associated with lower likelihood of glaucomatous optic neuropathy. However, consumption levels of total PUFAs in the higher quartiles were associated with a higher risk of glaucoma, which may have resulted from the relative intakes of ω-6 and ω-3 fatty acids and other confounding comorbidities. This study also hypothesizes that increasing the proportion of dietary ω-3 consumption levels while controlling overall daily PUFA intake may be protective against glaucoma. However, longitudinal studies or randomized clinical trials are needed to assess these hypotheses.

Purpose There are no reported large series of trabeculectomy with mitomycin-C (MMC) in Western patients with primary angle-closure glaucoma (PACG). Our study evaluates long-term tonometric outcomes of trabeculectomy in PACG. Materials and methods This is a retrospective cohort study. The primary outcomes were the Kaplan-Meier success rates on survival analyses using 3 criteria, with or without adjunctive medication: (A) intraocular pressure (IOP) ≤18 mm Hg and IOP reduction of 20%; (B) IOP≤15 mm Hg and IOP reduction 25%; and (C) IOP≤12 mm Hg and IOP reduction 30%. In total, 136 eyes (102 patients) with PACG who underwent trabeculectomy MMC were included. The Cox proportional hazard regression analysis was used to identify risk factors for failure with multivariate analysis (P Results The qualified success rates (±SD) after 1, 3, and 5 years of follow-up for criterion A were 92% (±2.2%), 78% (±3.8%), and 72% (±4.3%); for criterion B, 86% (±3.0%), 65% (±4.4%), and 59% (±4.7%); and for criterion C, 62% (±4.2%), 40% (±4.5%), and 32% (±4.4%). Baseline factors associated with failure were: family history, absence of laser peripheral iridotomy, higher IOP, and presence of a crystalline lens. Conclusions Trabeculectomy with MMC effectively reduces IOP in PACG. Long-term IOP reduction is achieved for target IOP levels in the mid-teens. Presence of a crystalline lens, lack of iridotomy and higher preoperative IOP were associated with higher risks of failure.

Purpose: To evaluate the relationship between the peripapillary retinal nerve fiber layer (RNFL) measurements with Spectral-domain Optical Coherence Tomography (OCT) and Age-related macular degeneration (AMD). Methods: Patients >60 years of age without glaucoma or record of intraocular pressure >21 mmHg and no systemic or intraocular diseases or treatment or surgical intervention that affected the RNFL underwent OCT measurement of the RNFL. The severity of AMD was staged with the Clinical Age-Related Maculopathy Staging System. The relationship between RNFL measurements and AMD stages of one eye per patient was analyzed. Results: Eighty-six eyes (46 patients) with AMD and no glaucoma or other exclusion criteria received OCT RNFL measurements. Nine eyes (10.5%) were excluded because of distorted peripapillary anatomy from exudative AMD (7 eyes) or failure of the RNFL segmentation algorithm (2 eyes). Mean age ± S.D. of the 43 patients analyzed was 81.2 ± 7.3 years. The mean stage ± S.D. of AMD of the 77 eyes was 3.77 ± 1.05. Higher stages of AMD were statistically significantly associated with lower average RNFL and inferior sector RNFL (p = 0.049, 0 0015, respectively). The association of inferior sector RNFL and AMD stage remained statistically significant after adjusting for age. Conclusions: Spectral domain OCT is generally useful in measuring the peripapillary RNFL in eyes with different stages of AMD. Higher stage of AMD is associated with thinner peripapillary RNFL, which may masquerade as early glaucomatous damage.