Evaluation of Optic Nerve Head Microcirculation in Open-Angle Glaucoma Patients with Unilateral Visual Field Defect.

INTRODUCTION: Microcirculation of optic nerve head (ONH) in open-angle glaucoma (OAG) patients with unilateral visual field (VF) loss has yet to be fully investigated, especially the perimetrically unaffected fellow eyes. METHODS: Thirty-eight OAG patients with VF defect in one eye and normal VF in the other eye, and thirty-one healthy participants were analyzed. All participants underwent laser speckle flowgraphy (LSFG), spectral-domain optical coherence tomography (SD-OCT) imaging, and VF test for further analyses. LSFG measurements included mean blur rate in all area of ONH (MA), big vessel area of ONH (MV), and tissue area of ONH (MT). SD-OCT parameters included circumpapillary retinal nerve fiber layer (cpRNFL) thickness and macula thicknesses. The difference of LSFG and SD-OCT indices between glaucoma patients and healthy controls were compared. The diagnostic accuracy was analyzed with the areas under the receiver operating characteristic curves (AROCs). RESULTS: Global cpRNFL thickness and macular thickness in unaffected eyes of OAG patients were higher than their fellow eyes and lower than healthy eyes. MA and MV in healthy eyes and unaffected eyes were significantly higher than in affected eyes. MT in unaffected eyes of OAG patients was higher than in their fellow affected eyes but lower than in healthy eyes. The AROCs were highest for cpRNFL (0.925), followed by macular thickness (0.838), and MT (0.834). CONCLUSIONS: ONH microcirculation in perimetrically unaffected fellow eyes was decreased in OAG patients with unilateral VF loss. LSFG can detect changes of ONH in high-risk eyes before detectable VF damage, which may reflect the vascular pathophysiology for glaucoma.

Risk Factors for Progression of Primary Open-Angle Glaucoma with Lower Normal Intraocular Pressure.

INTRODUCTION: This study aimed to investigate intraocular pressure (IOP)-independent factors associated with the progression of primary open-angle glaucoma (POAG) with IOP ≤15 mm Hg. METHODS: POAG patients with maximum IOP ≤15 mm Hg at the Kyoto University Hospital between January 2011 and August 2021 were retrospectively enrolled. We evaluated effects of various factors on the rate of mean deviation (MD) changes in the visual field (VF) examinations using a linear mixed model. These factors included hypertension, diabetes mellitus (DM), hyperlipidemia (HL), cardiovascular disease, arrhythmia, disc hemorrhage, sleep apnea syndrome, orthopedic diseases, and malignant tumors. RESULTS: In total, 98 eyes from 68 patients were included. The baseline MD was -9.74 ± 7.85 dB. The mean rate of MD change and IOP during the observation period were -0.28 ± 0.04 dB/year and 11.8 ± 1.0 mm Hg, respectively. Comorbidity of DM or HL showed a significant positive association with the rate of MD change (ß = 0.35, p = 0.0006 and ß = 0.18, p = 0.036, respectively) in the model adjusted for age, sex, axial length, mean IOP, and standard deviation of IOP during the observation period. However, no significant association of DM or HL was found after adjusting for central corneal thickness. CONCLUSION: This study suggests that DM or HL is associated with VF deterioration in glaucoma with lower IOP, but the association may be due to differences in IOP characteristics.

Clinical Characteristics of Microcystic Macular Edema in Chronic Primary Angle-Closure Glaucoma and Primary Open-Angle Glaucoma Patients.

INTRODUCTION: This study investigated the clinical characteristics of and risk factors for microcystic macular edema (MME) in patients with chronic primary angle-closure glaucoma (CPACG) and primary open-angle glaucoma (POAG). METHODS: This retrospective observational study included 1,588 eyes from 926 glaucoma inpatients and analyzed the patients' basic demographic information, visual field parameters, macular scans, and peripapillary retinal nerve fiber layer thickness. RESULTS: Our findings were that the incidence rate of MME was 3.97% (34/857) in CPACG and 5.88% (43/731) in POAG. MME was predominantly diagnosed at an advanced stage in CPACG (almost 100%) compared to POAG (93.02%). MME was most frequently involved in the inferior (83.12%) quadrant of the peri-macular region in both CPACG and POAG. Risk factors for MME occurrence in CPACG and POAG included lower visual field mean deviation (OR = 1.14, 95%: CI 1.05-1.24, p = 0.003; OR = 1.14, 95% CI: 1.06-1.21, p < 0.001) and younger age (OR = 0.92, 95% CI: 0.88-0.96, p < 0.001; OR = 0.96, 95% CI: 0.93-0.99, p = 0.003), while female sex (OR = 0.30, 95% CI: 0.11-0.84, p = 0.022) reduced the MME occurrence in POAG. CONCLUSION: MME could develop in both CPACG and POAG patients, occurring earlier in POAG. The inferior peri-macular region is commonly affected. Younger age and poorer visual field are risk factors for MME in glaucoma patients.

Border tissue morphology is associated with the pattern of visual field progression in open-angle glaucoma.

The etiology of open-angle glaucoma (OAG) is yet unclear. This study investigated possible risk factors, such as the morphology of the border tissue that affect the pattern of visual field (VF) progression in eyes with OAG. 166 eyes of 166 OAG patients with an externally oblique border tissue (EOBT) at least in one direction were included. EOBT was obtained by analyzing enhanced depth imaging spectral-domain optical coherence tomography images. A pointwise linear regression was used to determine VF progression by measuring the deterioration rate of each point in the VF. The odds ratio of VF progression for each risk factor was estimated using logistic regression analysis. Seventy (42.2%) eyes showed VF deterioration. In multivariate analysis, longer follow-up period, higher baseline intraocular pressure (IOP), lower mean ocular perfusion pressure (MOPP), and smaller angular location of the longest EOBT were associated with VF progression (all p values were below 0.05). In the multivariate analysis, the location of the longest EOBT was significantly associated with inferior (p = 0.002) and central (p = 0.017) VF progression. In conclusion, VF progression pattern in OAG eyes is associated with the location of the longest EOBT as well as other known risk factors.

Infrared- and white-light retinal sensitivity in glaucomatous neuropathy.

Glaucoma causes irreversible neuropathy, which, untreated, may lead to blindness. In this case-control study, we measured two-photon infrared (IR) light sensitivity in glaucomatous eyes to propose a new method to quantify the visual loss. In total, 64 patients were recruited with an equal distribution between glaucoma and control groups. Retinal sensitivity to IR light was assessed using a two-photon excitation device. A fundus-driven microperimeter was used to measure retinal sensitivity to visible light. The retinal nerve fiber layer (RNFL) thickness was quantified automatically with optical coherence tomography. The IR sensitivity of glaucoma and control eyes differed significantly (P = .003): 9.8 (6.5 to 13.1) dB vs. 10.9 (8.2 to 13.0) dB. Although in the visible-light microperimetry, retinal sensitivity was decreased in glaucoma (17.0, range: 6.9 to 20.0 dB) compared to the controls (17.7, range: 11.6 to 20.0 dB), this difference did not reach the significance level. A significant thinning of the RNFL in the glaucoma group was observed (P < .001). IR sensitivity significantly correlated with the RNFL in three of the four assessed quadrants instead of only one in visible-light microperimetry. Although further research is needed, this proof-of-concept study suggests that IR-light sensitivity can be used to support the detection of glaucomatous neuropathy.

Identifying the Retinal Layers Linked to Human Contrast Sensitivity Via Deep Learning.

Purpose: Luminance contrast is the fundamental building block of human spatial vision. Therefore contrast sensitivity, the reciprocal of contrast threshold required for target detection, has been a barometer of human visual function. Although retinal ganglion cells (RGCs) are known to be involved in contrast coding, it still remains unknown whether the retinal layers containing RGCs are linked to a person's contrast sensitivity (e.g., Pelli-Robson contrast sensitivity) and, if so, to what extent the retinal layers are related to behavioral contrast sensitivity. Thus the current study aims to identify the retinal layers and features critical for predicting a person's contrast sensitivity via deep learning. Methods: Data were collected from 225 subjects including individuals with either glaucoma, age-related macular degeneration, or normal vision. A deep convolutional neural network trained to predict a person's Pelli-Robson contrast sensitivity from structural retinal images measured with optical coherence tomography was used. Then, activation maps that represent the critical features learned by the network for the output prediction were computed. Results: The thickness of both ganglion cell and inner plexiform layers, reflecting RGC counts, were found to be significantly correlated with contrast sensitivity (r = 0.26 ∼ 0.58, Ps < 0.001 for different eccentricities). Importantly, the results showed that retinal layers containing RGCs were the critical features the network uses to predict a person's contrast sensitivity (an average R2 = 0.36 ± 0.10). Conclusions: The findings confirmed the structure and function relationship for contrast sensitivity while highlighting the role of RGC density for human contrast sensitivity.

Multi-Contrast Magnetic Resonance Imaging of Visual White Matter Pathways in Patients With Glaucoma.

Purpose: Glaucoma is a disorder that involves visual field loss caused by retinal ganglion cell damage. Previous diffusion magnetic resonance imaging (dMRI) studies have demonstrated that retinal ganglion cell damage affects tissues in the optic tract (OT) and optic radiation (OR). However, because previous studies have used a simple diffusion tensor model to analyze dMRI data, the microstructural interpretation of white matter tissue changes remains uncertain. In this study, we used a multi-contrast MRI approach to further clarify the type of microstructural damage that occurs in patients with glaucoma. Methods: We collected dMRI data from 17 patients with glaucoma and 30 controls using 3-tesla (3T) MRI. Using the dMRI data, we estimated three types of tissue property metrics: intracellular volume fraction (ICVF), orientation dispersion index (ODI), and isotropic volume fraction (IsoV). Quantitative T1 (qT1) data, which may be relatively specific to myelin, were collected from all subjects. Results: In the OT, all four metrics showed significant differences between the glaucoma and control groups. In the OR, only the ICVF showed significant between-group differences. ICVF was significantly correlated with qT1 in the OR of the glaucoma group, although qT1 did not show any abnormality at the group level. Conclusions: Our results suggest that, at the group level, tissue changes in OR caused by glaucoma might be explained by axonal damage, which is reflected in the intracellular diffusion signals, rather than myelin damage. The significant correlation between ICVF and qT1 suggests that myelin damage might also occur in a smaller number of severe cases.

The Association among Blood Pressure, Blood Pressure Medications, and Glaucoma in a Nationwide Electronic Health Records Database.

PURPOSE: To measure the association among blood pressure (BP), BP medications, and glaucoma using the All of Us Research Program database. DESIGN: A retrospective, longitudinal cohort study leveraging a national electronic health record (EHR) database administered by the National Institutes of Health. PARTICIPANTS: Eye patients in the All of Us Research Program database with at least 15 months of follow-up and 1 BP measurement. METHODS: Univariable and multivariable Cox regression models predicted the risk of developing incident open-angle glaucoma (OAG). Mean arterial pressure (MAP) and the number of BP medication classes were entered as time-varying predictors to account for changes over time. MAIN OUTCOME MEASURES: The risk of developing incident OAG, as defined by billing diagnosis codes. RESULTS: Of 20 815 eligible eye patients who qualified for this study, 462 developed OAG. Low BP (MAP < 83.0 mmHg) was associated with increased risk of developing OAG (hazard ratio [HR], 1.32; 95% confidence interval [CI], 1.04-1.67). High BP (MAP > 101.3 mmHg) and the number of BP medication classes were not associated with OAG after adjustment for covariates. Other risk factors associated with OAG included being Black (HR, 3.31, 95% CI, 2.63-4.17), Hispanic or Latino (HR, 2.53, 95% CI, 1.94-3.28), Asian (HR, 2.22, 95% CI, 1.24-3.97), older in age (80+ years, HR, 20.1, 95% CI, 9.10-44.5), and diabetic (HR, 1.32, 95% CI, 1.04-1.67). Female gender was associated with decreased hazard of developing OAG (HR, 0.66, 95% CI, 0.55-0.80). No significant interaction was observed between MAP and the number of BP medications on the risk of developing OAG. CONCLUSIONS: We found that low BP is associated with increased risk of developing OAG in a national longitudinal EHR database. We did not find evidence supporting a differential effect of medically treated and untreated low BP. This study adds to the body of literature implicating vascular dysregulation as a potential etiology for the development of OAG, particularly emphasizing the lack of influence of BP medications on this relationship.

Open-source deep learning-based automatic segmentation of mouse Schlemm's canal in optical coherence tomography images.

The purpose of this study was to develop an automatic deep learning-based approach and corresponding free, open-source software to perform segmentation of the Schlemm's canal (SC) lumen in optical coherence tomography (OCT) scans of living mouse eyes. A novel convolutional neural network (CNN) for semantic segmentation grounded in a U-Net architecture was developed by incorporating a late fusion scheme, multi-scale input image pyramid, dilated residual convolution blocks, and attention-gating. 163 pairs of intensity and speckle variance (SV) OCT B-scans acquired from 32 living mouse eyes were used for training, validation, and testing of this CNN model for segmentation of the SC lumen. The proposed model achieved a mean Dice Similarity Coefficient (DSC) of 0.694 ± 0.256 and median DSC of 0.791, while manual segmentation performed by a second expert grader achieved a mean and median DSC of 0.713 ± 0.209 and 0.763, respectively. This work presents the first automatic method for segmentation of the SC lumen in OCT images of living mouse eyes. The performance of the proposed model is comparable to the performance of a second human grader. Open-source automatic software for segmentation of the SC lumen is expected to accelerate experiments for studying treatment efficacy of new drugs affecting intraocular pressure and related diseases such as glaucoma, which present as changes in the SC area.

The Effect of Achieving Target Intraocular Pressure on Visual Field Worsening.

PURPOSE: To estimate the effect of achieving target intraocular pressure (IOP) values on visual field (VF) worsening in a treated clinical population. DESIGN: Retrospective analysis of longitudinal data. PARTICIPANTS: A total of 2852 eyes of 1688 patients with glaucoma-related diagnoses treated in a tertiary care practice. All included eyes had at least 5 reliable VF tests and 5 IOP measures on separate visits along with at least 1 target IOP defined by a clinician on the first or second visit. METHODS: The primary dependent variable was the slope of the mean deviation (MD) over time (decibels [dB]/year). The primary independent variable was mean target difference (measured IOP - target IOP). We created simple linear regression models and mixed-effects linear models to study the relationship between MD slope and mean target difference for individual eyes. In the mixed-effects models, we included an interaction term to account for disease severity (mild/suspect, moderate, or advanced) and a spline term to account for the differing effects of achieving target IOP (target difference ≤0) and failing to achieve target IOP (target difference >0). MAIN OUTCOME MEASURES: Rate of change in MD slope (changes in dB/year) per 1 mmHg change in target difference at different stages of glaucoma severity. RESULTS: Across all eyes, a simple linear regression model demonstrated that a 1 mmHg increase in target difference had a -0.018 dB/year (confidence interval [CI], -0.026 to -0.011; P < 0.05) effect on MD slope. The mixed-effects model shows that eyes with moderate disease that fail to achieve their target IOP experience the largest effects, with a 1 mmHg increase in target difference resulting in a -0.119 dB/year (CI, -0.168 to -0.070; P < 0.05) worse MD slope. The effects of missing target IOP on VF worsening were more pronounced than the effect of absolute level of IOP on VF worsening, where a 1 mmHg increase in IOP had a -0.004 dB/year (CI, -0.011 to 0.003; P > 0.05) effect on the MD slope. CONCLUSIONS: In treated patients, failing to achieve target IOP was associated with more rapid VF worsening. Eyes with moderate glaucoma experienced the greatest VF worsening from failing to achieve target IOP.

Measuring optic nerve head perfusion to monitor glaucoma: a study on structure-function relationships using laser speckle flowgraphy.

PURPOSE: We aimed to describe the global and localized correlations among visual field (VF) sensitivity, optic nerve head (ONH) perfusion measured by laser speckle flowgraphy (LSFG) and neural structure measured by optical coherence tomography (OCT) in open-angle glaucoma (OAG) and to compare the floor effect for LSFG and OCT. METHODS: Cross-sectional, multicenter study including one eye each from fifty OAG patients (mean age 69.3 years; average VF mean deviation, MD, -8.5 dB, range -25.17 to 0.85 dB) and fifty-one controls. Patients underwent SITA standard 24-2 automated perimetry and measurement of ONH perfusion, peripapillary retinal nerve fibre layer thickness (RNFLT) and macular ganglion cell-inner plexiform layer thickness (GCIPLT). We tested the presence of a significant change (breakpoint) in the correlation slope with VF sensitivity to assess floor effect. RESULTS: The correlation between the LSFG parameter Mean All (MA) of the global disc area and MD (r = 0.56, p < 0.001) did not show a breakpoint, in contrast to the correlations between MD and OCT global parameters, which showed breakpoints at -8.53 and -4.05 dB for RNFLT and GCIPLT, respectively. Global and localized correlations with VF sensitivity were stronger for LSFG compared to OCT. In particular, LSFG outperformed OCT in the correlation with the central VF sector (r = 0.50, p < 0.001 and r = 0.06, p = 0.67 for MA and RNFLT, respectively). CONCLUSION: The global and sectoral correlations with VF sensitivity and the favourable floor effect compared to OCT indicate LSFG as a promising tool to monitor progression particularly in late-stage glaucoma. Further longitudinal studies are warranted.

Anterior-segment optical coherence tomography of filtering blebs in the early postoperative period of ab externo SIBS microshunt implantation with mitomycin C: Morphological analysis and correlation with intraocular pressure reduction.

PURPOSE: To analyse the morphological evolution of filtering blebs with anterior-segment OCT (AS-OCT) and its correlation with intraocular pressure after ab externo SIBS microshunt implantation with mitomycin C (MMC) during a 3-month follow-up period. METHODS: Twenty-eight filtering blebs of 28 patients with open-angle glaucoma were measured horizontally and vertically in the sub-Tenon space with AS-OCT after ab externo SIBS microshunt implantation with MMC. The intraocular pressure (IOP) was monitored simultaneously at each visit. Maturation of and morphological changes in the blebs and correlations with the IOP were recorded. RESULTS: The average median preoperative IOP of 20.7 (range, 12-30) mmHg decreased to 8.5 (range, 4-17), 8.9 (range, 5-17), 10.4 (range, 8-16) and 10.9 (range, 9-15) mmHg at 24 hr, 1 week, 1 month and 3 months, respectively (p < 0.001). A multiform morphology on AS-OCT prevailed at all time points, with a 3.5% rate of a uniform bleb morphology at the first week. The horizontal and vertical diameters of the blebs increased from baseline to the third month. The horizontal expansion (406 ± 127 µm on day 7, p = 0.04, 712 ± 211 µm on day 30, p = 0.02 and 952 ± 218 µm on day 90, p < 0.001) was greater than the vertical expansion (16 ± 18 µm, p = 0.3 on day 1, 63 ± 27 µm, p = 0.02 on day 30 and 137 ± 34 µm, p < 0.001 on day 90) without correlation with the IOP (r = -0.3, p = 0.2). CONCLUSION: Anterior-segment OCT (AS-OCT) of the filtering blebs formed after ab externo SIBS microshunt implantation showed progressive horizontal and vertical expansion of the blebs in the sub-Tenon space, with a significant peak at the first month not significantly correlated with the decrease in the IOP.

The effects of visual field loss from glaucoma on performance in a driving simulator.

BACKGROUND: To examine the effects of different stages of visual field loss (VFL) from advanced glaucoma on performance in a driving simulator. METHODS: Data on performance and safety from a traffic simulator test for 104 participants with withdrawn driver's licences due to visual field loss from advanced glaucoma were compared with data from 83 individuals without visual deficits in a cross-sectional study. Individuals with glaucoma that regained their driving licences after a successful simulator test were then followed in a national accident database. RESULTS: Glaucoma participants passed the test in 71% (95% confidence interval 61-79%) of the cases. Younger participants were more successful than older. No significant differences on safety or performance measures were detected between glaucoma- and normally sighted participants. Compared with passed glaucoma participants, failed glaucoma participants had more collisions, more critical failed to give way events, longer time headways, and longer reaction times. This group had also a higher extent of central visual field loss. None of the participants with a regained licence were involved in a motor vehicle accident during the 2 to 4 year follow-up after the simulator test. CONCLUSION: Severity of glaucoma predicts driver safety on a group level. However, even individuals with severe visual field loss from glaucoma might drive safely, which highlights the need for individual assessments for licencing purposes.

Parapapillary deep-layer microvasculature dropout is only found near the retinal nerve fibre layer defect location in open-angle glaucoma.

PURPOSE: We aimed to investigate the topographic correspondence between deep-layer microvasculature dropout (MvD) and retinal nerve fibre layer (RNFL) defects in eyes with open-angle glaucoma (OAG) using spectral-domain optical coherence tomography (SD-OCT) and optical coherence tomography angiography (OCT-A). METHODS: Microvasculature dropout width and location were determined using OCT-A, RNFL thickness, RNFL defect width and location were revealed using SD-OCT. The association between MvD and RNFL widths and that between the location of the MvD and RNFL defects were investigated. In addition, patients with OAG were divided into two groups: the RNFL defect in one hemiretina (RNFLD-HR) group (n = 24 eyes) and the RNFL defects in both hemiretinas (RNFLD-BR) group (n = 25 eyes). The presence, width and location of MvDs were compared between the two groups. RESULTS: Forty-nine eyes were included. In 24 RNFLD-HR eyes, all MvDs were found in the inferior area, corresponding with the location of the RNFL defect. Meanwhile, in 25 RNFLD-BR eyes, 18 MvDs (72%) were found in the inferior hemiretina, two (8%) were found in the superior hemiretina, and five (20%) were found in both hemiretinas. In RNFLD-BR eyes, the average RNFL thickness was thinner in a location with MvD than a location without MvD. CONCLUSION: Considering that MvD is only observed at the location of the RNFL defect in RNFLD-HR eyes and is usually found in the location of more severe RNFL defects in RNFLD-BR eyes, MvD seems to be a sign that accompanies glaucomatous damage in OAG eyes.

Statin use and the reoperation rates in glaucoma filtration surgery - population-based cohort study.

PURPOSE: To examine the association of systemic statin therapy and reoperation rate after glaucoma filtration surgery (GFS). METHODS: This is a population-based, historic cohort study of 2705 eyes undergoing GFS in Finland between July 2009 and December 2016. GFSs were identified from national administrative healthcare registers. Baseline sociodemographic and health characteristics were documented. Reoperation rates of GFS subgroups were analysed, with statin users compared to non-users. The outcomes were modelled using a Poisson regression model adjusted for age, sex, education, statin use, chronic comorbidities, and cataract surgery with incident rate ratios (IRR) as the main outcome measure. RESULTS: The cohort contained 2263 subjects with open-angle glaucoma (OAG), 823 men and 1440 women. Surgery was performed on 2705 eyes. First documented procedures: deep sclerectomy (DS) (n = 1601), trabeculectomy (TRE) (799) and glaucoma drainage device (GDD) implantation (305) respectively. In total, 438 secondary operations were performed during the 7.5-year (median 2.25 years) follow-up period. The reoperation rates were 19% after DS, 12% after TRE, and 13% after GDD. Of the surgical procedures, 32% were performed on eyes of patients receiving statin therapy. Statin users showed no difference in reoperation rates (IRR 1.06, CI 0.82-1.37). In subgroups, no difference was observed in the reoperation rates adjusted with statin use after filtration surgery (DS, TRE) (IRR 1.06, CI 0.8-1.40) or GDD implantation (0.57, CI 0.20-1.63). CONCLUSION: Systemic statin therapy among surgically treated OAG patients had no impact on secondary surgery rates following DS, TRE or GDD implantation.

Three-year effectiveness and safety of the XEN gel stent as a solo procedure or in combination with phacoemulsification in open-angle glaucoma: a multicentre study.

PURPOSE: To assess the 3-year effectiveness and safety of the XEN gel stent implanted ab interno in open-angle glaucoma (OAG). METHODS: This study was a multicentre, retrospective chart review of consecutive patients with OAG who underwent ab-interno gel stent placement alone or combined with phacoemulsification between 1 January 2014 and 1 October 2015. Outcome measures included mean changes in intraocular pressure (IOP) and IOP-lowering medication count from medicated baseline at 1, 2, 3 (primary outcome) and 4 years (if available) postimplantation. Intraoperative complications, adverse events of special interest (AESIs) and secondary surgical interventions (SSIs) were recorded. RESULTS: The safety and effectiveness populations included 212 eyes (primary and secondary) and 174 eyes (primary), respectively. Mean IOP and medication decreased from 20.7 mmHg and 2.5 at baseline (n = 163 primary/first implanted eyes) to 13.9 mmHg and 1.1 medications (n = 76) at 3 years postimplantation, respectively. Mean changes from baseline in IOP (-5.6, -6.2 and -6.6 mmHg) and IOP-lowering medication count (-1.8, -1.6 and -1.4) were statistically significant at 1, 2 and 3 years postimplantation, respectively. Results appeared comparable when implantation was performed with (n = 76) or without (n = 98) phacoemulsification. In primary eyes with 4-year IOP and medication count data (n = 27), mean IOP was 14.0 mmHg on 1.3 medications at 4 years postimplantation. Fifteen (7.1%) eyes had intraoperative complications, 31 (14.6%) experienced 46 postoperative AESIs, and 26 (12.3%) required SSI. CONCLUSION: The gel stent effectively lowered IOP and IOP-lowering medication count over 3 years, with a predictable and acceptable safety profile, when implanted via the traditional ab-interno technique.

Multimodal Machine Learning Using Visual Fields and Peripapillary Circular OCT Scans in Detection of Glaucomatous Optic Neuropathy.

PURPOSE: To develop and validate a multimodal artificial intelligence algorithm, FusionNet, using the pattern deviation probability plots from visual field (VF) reports and circular peripapillary OCT scans to detect glaucomatous optic neuropathy (GON). DESIGN: Cross-sectional study. SUBJECTS: Two thousand four hundred sixty-three pairs of VF and OCT images from 1083 patients. METHODS: FusionNet based on bimodal input of VF and OCT paired data was developed to detect GON. Visual field data were collected using the Humphrey Field Analyzer (HFA). OCT images were collected from 3 types of devices (DRI-OCT, Cirrus OCT, and Spectralis). Two thousand four hundred sixty-three pairs of VF and OCT images were divided into 4 datasets: 1567 for training (HFA and DRI-OCT), 441 for primary validation (HFA and DRI-OCT), 255 for the internal test (HFA and Cirrus OCT), and 200 for the external test set (HFA and Spectralis). GON was defined as retinal nerve fiber layer thinning with corresponding VF defects. MAIN OUTCOME MEASURES: Diagnostic performance of FusionNet compared with that of VFNet (with VF data as input) and OCTNet (with OCT data as input). RESULTS: FusionNet achieved an area under the receiver operating characteristic curve (AUC) of 0.950 (0.931-0.968) and outperformed VFNet (AUC, 0.868 [95% confidence interval (CI), 0.834-0.902]), OCTNet (AUC, 0.809 [95% CI, 0.768-0.850]), and 2 glaucoma specialists (glaucoma specialist 1: AUC, 0.882 [95% CI, 0.847-0.917]; glaucoma specialist 2: AUC, 0.883 [95% CI, 0.849-0.918]) in the primary validation set. In the internal and external test sets, the performances of FusionNet were also superior to VFNet and OCTNet (FusionNet vs VFNet vs OCTNet: internal test set 0.917 vs 0.854 vs 0.811; external test set 0.873 vs 0.772 vs 0.785). No significant difference was found between the 2 glaucoma specialists and FusionNet in the internal and external test sets, except for glaucoma specialist 2 (AUC, 0.858 [95% CI, 0.805-0.912]) in the internal test set. CONCLUSIONS: FusionNet, developed using paired VF and OCT data, demonstrated superior performance to both VFNet and OCTNet in detecting GON, suggesting that multimodal machine learning models are valuable in detecting GON.

The RNA-binding protein and stress granule component ATAXIN-2 is expressed in mouse and human tissues associated with glaucoma pathogenesis.

Polyglutamine repeat expansions in the Ataxin-2 (ATXN2) gene were first implicated in Spinocerebellar Ataxia Type 2, a disease associated with degeneration of motor neurons and Purkinje cells. Recent studies linked single nucleotide polymorphisms in the gene to elevated intraocular pressure in primary open angle glaucoma (POAG); yet, the localization of ATXN2 across glaucoma-relevant tissues of the vertebrate eye has not been thoroughly examined. This study characterizes ATXN2 expression in the mouse and human retina, and anterior eye, using an antibody validated in ATXN2-/- retinas. ATXN2-ir was localized to cytosolic sub compartments in retinal ganglion cell (RGC) somata and proximal dendrites in addition to GABAergic, glycinergic, and cholinergic amacrine cells in the inner plexiform layer (IPL) and displaced amacrine cells. Human, but not mouse retinas showed modest immunolabeling of bipolar cells. ATXN2 immunofluorescence was prominent in the trabecular meshwork and pigmented and nonpigmented cells of the ciliary body, with analyses of primary human trabecular meshwork cells confirming the finding. The expression of ATXN2 in key POAG-relevant ocular tissues supports the potential role in autophagy and stress granule formation in response to ocular hypertension.

Microvasculature Recovery Detected Using Optical Coherence Tomography Angiography and the Rate of Visual Field Progression After Glaucoma Surgery.

Purpose: We evaluated microvascular changes using optical coherence tomography angiography (OCT-A) in glaucoma patients who underwent glaucoma surgery. Methods: The macula and optic nerve head were imaged using an OCT-A device at one day before surgery and at one week, one month, three months, and six months after surgery. Measurements of vessel density (VD) were made in the intradisc region and macula, and the area of the foveal avascular zone (FAZ) was measured in both superficial and deep vascular layers. A mean deviation (MD) slope value of < -1.0 decibel/y was considered to be indicative of VF progression. Results: A significant increase in VD was observed postoperatively in the deep vascular layer of the intradisc area (P < 0.001), and a significant decrease in the FAZ area was evident in the deep vascular layer (P = 0.018). An increase in the intradisc deep VD (17.48% ± 5.63%) was statistically significant in glaucoma eyes without progression, compared with those with progression (-1.27% ± 2.19%). Worse preoperative MD of the VF (P = 0.006), lower preoperative intradisc VD (P < 0.001), and fewer changes in the intradisc deep VD after surgery (P < 0.001) were significantly associated with MD slope. Conclusions: We found deep VD changes in the laminar region of the optic nerve head and the macular area at up to postoperative one month after glaucoma surgery. An increase in the deep VD in the laminar region was beneficial to VF progression in glaucoma patients after surgery.