Reproducibility of consecutive automated telemetric noctodiurnal IOP profiles as determined by an intraocular implant.

BACKGROUND: Intraocular pressure (IOP) monitoring in glaucoma management is evolving with novel devices. We investigated the reproducibility of 24 hour profiles on two consecutive days and after 30 days of self-measurements via telemetric IOP monitoring. METHODS: Seven primary patients with open-angle glaucoma previously implanted with a telemetric IOP sensor in one eye underwent automatic measurements throughout 24 hours on two consecutive days ('day 1' and 'day 2'). Patients wore an antenna adjacent to the study eye connected to a reader device to record IOP every 5 min. Also, self-measurements in six of seven patients were collected for a period of 30 days. Analysis included calculation of hourly averages to correlate time-pairs of day 1 versus day 2 and the self-measurements vers day 2. RESULTS: The number of IOP measurements per patient ranged between 151 and 268 on day 1, 175 and 268 on day 2 and 19 and 1236 during 30 days of self-measurements. IOP time-pairs of automatic measurements on day 1 and day 2 were significantly correlated at the group level (R=0.83, p<0.001) and in four individual patients (1, 2, 6 and 7). IOP time-pairs of self-measurements and day 2 were significantly correlated at the group level (R=0.4, p<0.001) and in four individual patients (2, 5, 6 and 7). CONCLUSIONS: Twenty-four hour automatic measurements of IOP are correlated on consecutive days and, though to a lesser degree, with self-measurements. Therefore a virtual 24-hour IOP curve might be constructed from self-measurements. Both options provide an alternative to frequent in-office IOP measurements.

Evaluation of an offline, artificial intelligence system for referable glaucoma screening using a smartphone-based fundus camera: a prospective study.

BACKGROUND/OBJECTIVES: An affordable and scalable screening model is critical for undetected glaucoma. The study evaluated the performance of an offline, smartphone-based AI system for the detection of referable glaucoma against two benchmarks: specialist diagnosis following full glaucoma workup and consensus image grading. SUBJECTS/METHODS: This prospective study (tertiary glaucoma centre, India) included 243 subjects with varying severity of glaucoma and control group without glaucoma. Disc-centred images were captured using a validated smartphone-based fundus camera analysed by the AI system and graded by specialists. Diagnostic ability of the AI in detecting referable Glaucoma (Confirmed glaucoma) and no referable Glaucoma (Suspects and No glaucoma) when compared to a final diagnosis (comprehensive glaucoma workup) and majority grading (image grading) by Glaucoma specialists (pre-defined criteria) were evaluated. RESULTS: The AI system demonstrated a sensitivity and specificity of 93.7% (95% CI: 87.6-96.9%) and 85.6% (95% CI:78.6-90.6%), respectively, in the detection of referable glaucoma when compared against final diagnosis following full glaucoma workup. True negative rate in definite non-glaucoma cases was 94.7% (95% CI: 87.2-97.9%). Amongst the false negatives were 4 early and 3 moderate glaucoma. When the same set of images provided to the AI was also provided to the specialists for image grading, specialists detected 60% (67/111) of true glaucoma cases versus a detection rate of 94% (104/111) by the AI. CONCLUSION: The AI tool showed robust performance when compared against a stringent benchmark. It had modest over-referral of normal subjects despite being challenged with fundus images alone. The next step involves a population-level assessment.

Factors affecting corneal deformation amplitude measured by Corvis ST in eyes with open-angle glaucoma.

PURPOSE: To evaluate the factors affecting corneal deformation amplitude (DA) measured using Corvis ST in eyes with open-angle glaucoma. METHODS: This prospective, longitudinal study included 48 eyes with open-angle glaucoma who required additional intraocular pressure (IOP)-lowering drops. All eyes underwent a complete eye examination at baseline, including a Corvis ST, which was repeated 4-8 weeks after the change in therapy. Factors affecting the corneal biomechanics, namely the DA, were determined using mixed effect models. RESULTS: The mean age of the cohort was 65.0 ± 7.9 years. The mean IOP reduced from 23.4 ± 5.4 mmHg to 17.9 ± 5 mmHg after the change in glaucoma treatment ( P < 0.001). The DA increased from 0.89 ± 0.16 mm to 1.00 ± 0.13 mm after IOP reduction ( P < 0.001). On mixed effect model analysis, IOP (-0.02 ± 0.001, P < 0.001) and corneal pachymetry (-0.0003 ± 0.0001, P = 0.02) affected the change in the DA. CONCLUSION: IOP and corneal pachymetry affect the DA and must be accounted for when using Corvis ST to evaluate corneal biomechanics in glaucoma.

XEN 45 Gel Stent Implantation in Open Angle Glaucoma: 5-Year Results of a Prospective Study.

PRCIS: XEN 45 Gel Stent is safe and effective for 3 years. The study results provide useful insight into the outcome of XEN 45 Gel Stent surgery over 5 years in daily clinical practice. PURPOSE: To evaluate 5-year outcomes of XEN 45 gel stent implantation (XEN) in patients with open angle glaucoma. METHODS: This is a prospective, single-center, interventional study. XEN implantation either alone (XEN) or combined with phacoemulsification (Phaco + XEN) was performed on 170 consecutive eyes (126 patients) with uncontrolled intraocular pressure (IOP) or disease progression despite medical treatment. "Complete" surgical success at 60 months was defined as unmedicated IOP ≤15 mm Hg and a relative IOP reduction ≥20% from medicated baseline, while "qualified" success allowed fewer ocular hypotensive medications than at baseline. Other definitions of success with various IOP targets were also analyzed. Secondary outcomes included mean IOP and IOP-lowering medication changes and rates of reoperations. RESULTS: Mean age was 78.1±9.2 years, and 70.3% were female. Mean medicated IOP decreased from 19.8±7.7 mm Hg [19.6±7.1 (XEN) vs. 19.8±7.0 mm Hg (Phaco+XEN)] at baseline to 12.6±3.1 mm Hg [12.5± 3.1 (XEN) vs. 12.6±3.1 (Phaco+XEN)] at 5 years (-37.0%; P < 0.001). Medications decreased from 2.0±1.3 [2.0±1.3 (XEN) vs. 2.0±1.3 (Phaco+XEN)] to 0.8±1.1 [0.8±1.1 (XEN) vs. 0.8±1.1 (Phaco + XEN)] (-60%; P <0.001). Needling was performed in 84 eyes (49%), and 19.4% underwent a secondary surgical intervention. Complete success at 3 years was a strong predictor of success at 5 years (odds ratio: 3.06, P <0.01), while needling was associated with higher rates of failure (odds ratio: 3.6, P <0.01). CONCLUSIONS: At 5 years, XEN gel stent implantation was a safe procedure and achieved clinically meaningful IOP and medication reduction. Success at 3 years is a predictor of success at 5 years. Needling correlates with higher failure rates.

Sustainable Enhanced Sodium-Ion Storage at Subzero Temperature with LiF Integration.

Though layered sodium oxide materials are identified as promising cathodes in sodium-ion batteries, biphasic P3/O3 depicts improved electrochemical performance and structural stability. Herein, a coexistent P3/O3 biphasic cathode material was synthesized with "LiF" integration, verified with X-ray diffraction and Rietveld refinement analysis. Furthermore, the presence of Li and F was deduced by inductively coupled plasma-optical emission spectrometry (ICP-OES) and energy dispersive X-ray spectroscopy (EDS). The biphasic P3/O3 cathode displayed an excellent capacity retention of 85% after 100 cycles (0.2C/30 mA g-1) at room temperature and 94% at -20 °C after 100 cycles (0.1C/15 mA g-1) with superior rate capability as compared to the pristine cathode. Furthermore, a full cell comprising a hard carbon anode and a biphasic cathode with 1 M NaPF6 electrolyte displayed excellent cyclic stabilities at a wider temperature range of -20 to 50 °C (with the energy density of 151.48 Wh kg-1) due to the enhanced structural stability, alleviated Jahn-Teller distortions, and rapid Na+ kinetics facilitating Na+ motion at various temperatures in sodium-ion batteries. The detailed post-characterization studies revealed that the incorporation of LiF accounts for facile Na+ kinetics, boosting the overall Na storage.

Non-polar ether-based electrolyte solutions for stable high-voltage non-aqueous lithium metal batteries.

The electrochemical instability of ether-based electrolyte solutions hinders their practical applications in high-voltage Li metal batteries. To circumvent this issue, here, we propose a dilution strategy to lose the Li+/solvent interaction and use the dilute non-aqueous electrolyte solution in high-voltage lithium metal batteries. We demonstrate that in a non-polar dipropyl ether (DPE)-based electrolyte solution with lithium bis(fluorosulfonyl) imide salt, the decomposition order of solvated species can be adjusted to promote the Li+/salt-derived anion clusters decomposition over free ether solvent molecules. This selective mechanism favors the formation of a robust cathode electrolyte interphase (CEI) and a solvent-deficient electric double-layer structure at the positive electrode interface. When the DPE-based electrolyte is tested in combination with a Li metal negative electrode (50 µm thick) and a LiNi0.8Co0.1Mn0.1O2-based positive electrode (3.3 mAh/cm2) in pouch cell configuration at 25 °C, a specific discharge capacity retention of about 74% after 150 cycles (0.33 and 1 mA/cm2 charge and discharge, respectively) is obtained.

Agreement of a Novel Artificial Intelligence Software With Optical Coherence Tomography and Manual Grading of the Optic Disc in Glaucoma.

PRCIS: The offline artificial intelligence (AI) on a smartphone-based fundus camera shows good agreement and correlation with the vertical cup-to-disc ratio (vCDR) from the spectral-domain optical coherence tomography (SD-OCT) and manual grading by experts. PURPOSE: The purpose of this study is to assess the agreement of vCDR measured by a new AI software from optic disc images obtained using a validated smartphone-based imaging device, with SD-OCT vCDR measurements, and manual grading by experts on a stereoscopic fundus camera. METHODS: In a prospective, cross-sectional study, participants above 18 years (Glaucoma and normal) underwent a dilated fundus evaluation, followed by optic disc imaging including a 42-degree monoscopic disc-centered image (Remidio NM-FOP-10), a 30-degree stereoscopic disc-centered image (Kowa nonmyd WX-3D desktop fundus camera), and disc analysis (Cirrus SD-OCT). Remidio FOP images were analyzed for vCDR using the new AI software, and Kowa stereoscopic images were manually graded by 3 fellowship-trained glaucoma specialists. RESULTS: We included 473 eyes of 244 participants. The vCDR values from the new AI software showed strong agreement with SD-OCT measurements [95% limits of agreement (LoA)=-0.13 to 0.16]. The agreement with SD-OCT was marginally better in eyes with higher vCDR (95% LoA=-0.15 to 0.12 for vCDR>0.8). Interclass correlation coefficient was 0.90 (95% CI, 0.88-0.91). The vCDR values from AI software showed a good correlation with the manual segmentation by experts (interclass correlation coefficient=0.89, 95% CI, 0.87-0.91) on stereoscopic images (95% LoA=-0.18 to 0.11) with agreement better for eyes with vCDR>0.8 (LoA=-0.12 to 0.08). CONCLUSIONS: The new AI software vCDR measurements had an excellent agreement and correlation with the SD-OCT and manual grading. The ability of the Medios AI to work offline, without requiring cloud-based inferencing, is an added advantage.

EYEMATE-SC Trial: Twelve-Month Safety, Performance, and Accuracy of a Suprachoroidal Sensor for Telemetric Measurement of Intraocular Pressure.

PURPOSE: Measuring and controlling intraocular pressure (IOP) provide the foundation for glaucoma treatment. Self-tonometry has been proposed as an alternative to measure IOP throughout the entire day better. The novel EYEMATE-SC sensor (Implandata) is implanted in the suprachoroidal space to enable contactless continual IOP monitoring. The aim of the present study was to investigate the 1-year safety, performance, and accuracy of the EYEMATE-SC in patients with primary open-angle glaucoma undergoing simultaneous nonpenetrating glaucoma surgery (NPGS). DESIGN: Prospective, multicenter, open-label, single-arm, interventional clinical trial. PARTICIPANTS: Twenty-four eyes of 24 patients with primary open-angle glaucoma who were due to undergo NPGS (canaloplasty or deep sclerectomy). METHODS: An EYEMATE-SC sensor was implanted during NPGS. Goldmann applanation tonometry (GAT) measurements were compared with the sensors' IOP measurements at all postoperative visits through 12 months. MAIN OUTCOME MEASURES: Device position and adverse events. RESULTS: Fifteen eyes underwent canaloplasty, and 9 underwent deep sclerectomy. Successful implantation of the sensor was achieved in all eyes with no reported intraoperative difficulties. Through the 12-month follow-up, no device migration, dislocation, or serious device-related complications were recorded. A total of 536 EYEMATE-SC measurements were pairwise included in the IOP agreement analysis. The overall mean difference between GAT and EYEMATE-SC measurements was 0.8 mmHg (95% confidence interval [CI] of the limits of agreement [LoA], -5.1 to 6.7 mmHg). The agreement gradually improved, and from 3 months after surgery until the end of the follow-up, the mean difference was -0.2 mmHg (95% CI of LoA, -4.6 to 4.2 mmHg) over a total of 264 EYEMATE-SC measurements, and 100% of measurements were within ±5 mmHg of GAT. CONCLUSIONS: The EYEMATE-SC sensor was safe and well tolerated through 12 months. Moreover, it allowed accurate, continuous IOP monitoring. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

Measurement of intraocular temperature in glaucoma: week-day and seasonal fluctuations.

PURPOSE: To evaluate long-term intraocular temperature (IOT) variations in eyes with primary open-angle glaucoma (POAG) using an intraocular telemetric sensor. METHODS: This prospective, open-label, multicentre observational study analysed the IOT variations in 22 eyes of 22 patients with POAG. All enrolled patients underwent implantation of an intraocular pressure (IOP) sensor during cataract surgery. The telemetric system uses a built-in temperature sensor to control measured IOP for temperature. Each time a patient measures their IOP, both the IOP and IOT are recorded in the reader device. Patients were instructed to self-measure their IOP as often as desired, but at least four times daily. Recorded readings were retrieved and analysed using mixed effect models and pairwise comparisons using Bonferroni correction to assess the statistical significance of average IOT variations between each individual weekday and calendar month. RESULTS: The mean age of patients was 67.8±6.8 years and 36.4% were women. A total of 132 745 readings over 21 102 measurement-days were obtained. On average, IOT was significantly higher on Sundays (34.57°C; 95% CI 34.37 to 34.78) than on any other day of the week (p<0.001). Mean IOT on other weekdays ranged from 34.48°C to 34.51°C. Over the year, IOT followed a clear seasonal pattern, reaching its maximum in July (34.8°C; 95% CI 34.56 to 34.97) and its minimum in January (34.4°C; 95% CI 34.15 to 34.56; p<0.001). CONCLUSIONS: This study demonstrates the feasibility of continual and long-term measurement of IOT using intraocular sensors. The results show significant short-term and long-term fluctuations of IOT. Research is warranted to understand the impact of IOT variations on IOP, ocular perfusion and glaucoma progression.

Safety and performance of a suprachoroidal sensor for telemetric measurement of intraocular pressure in the EYEMATE-SC trial.

AIM: To investigate the safety and performance of a telemetric suprachoroidal intraocular pressure (IOP) sensor (EYEMATE-SC) and the accuracy of its IOP measurements in open angle glaucoma (OAG) patients undergoing simultaneous non-penetrating glaucoma surgery (NPGS). METHODS: Prospective, multicentre, open-label, single-arm, interventional clinical trial. Twenty-four eyes of 24 patients with OAG regularly scheduled for NPGS (canaloplasty or deep sclerectomy) were simultaneously implanted with an EYEMATE-SC sensor. Six-month follow-up on the sensor's safety and performance as well as on the level of agreement between the EYEMATE-SC measurements and IOP measurements with Goldmann applanation tonometry (GAT). RESULTS: The eyes underwent canaloplasty (n=15) or deep sclerectomy (n=9) and achieved successful implantation of the sensor. No device migration, dislocation or serious device-related complications occurred. A total of 367 comparisons were included in the IOP agreement analysis. The overall mean difference between GAT and EYEMATE-SC measurements was 1.31 mm Hg (lower limit of agreement (LoA) 7.55 mm Hg; upper LoA -4.92 mm Hg). The maximum difference of 2.5 mm Hg ±3.96 (LoA 0.30-2.29) was reached on day 10 and continuously improved to an agreement of -0.15 mm Hg ±2.28 (LoA -1.24 to 0.89) after 6 months. Accordingly, the percentage of eyes within an IOP difference of ±5 mm Hg improved from 78% (day 3) to 100% (6 months). CONCLUSIONS: After 6 months, the EYEMATE-SC sensor was safe and well tolerated, and allowed continual IOP monitoring. TRIAL REGISTRATION NUMBER: NCT03756662.

Novel alendronate-CGS21680 conjugate reduces bone resorption and induces new bone formation in post-menopausal osteoporosis and inflammatory osteolysis mouse models.

Loss of bone is a common medical problem and, while it can be treated with available therapies, some of these therapies have critical side effects. We have previously demonstrated that CGS21680, a selective A2A adenosine receptor agonist, prevents bone loss, but its on-target toxicities (hypotension, tachycardia) and frequent dosing requirements make it unusable in the clinic. We therefore generated a novel alendronate-CGS21680 conjugate (MRS7216), to target the agonist to bone where it remains for long periods thereby diminishing the frequency of administration and curtailing side effects. MRS7216 was synthesized from CGS21680 by sequential activation of the carboxylic acid moiety and reacting with an appropriate amino acid (PEG, alendronic acid) under basic conditions. MRS7216 was tested on C57BL/6J (WT) mice with established osteoporosis (OP) and WT or A2A KO mice with wear particle-induced inflammatory osteolysis (OL). Mice were treated weekly with MRS7216 (10mg/kg). Bone formation was studied after in vivo labeling with calcein/Alizarin Red, and µCT and histology analyses were performed. In addition, human primary osteoblasts and osteoclasts were cultured using bone marrow discarded after hip replacement. Receptor binding studies demonstrate that MRS7216 efficiently binds the A2A adenosine receptor. MRS7216-treated OP and OL mice had significant new bone formation and reduced bone loss compared to vehicle or alendronate-treated mice. Histological analysis showed that MRS7216 treatment significantly reduced osteoclast number and increased osteoblast number in murine models. Interestingly, cultured human osteoclast differentiation was inhibited, and osteoblast differentiation was stimulated by the compound indicating that MRS7216 conjugates represent a novel therapeutic approach to treat osteoporosis and osteolysis.

The Importance of Signal Strength Index in Optical Coherence Tomography Angiography: A Study of Eyes with Pseudoexfoliation Syndrome.

Purpose: To evaluate the effect of the signal strength index (SSI) on a comparison of the vascular and structural OCT measurements between eyes with pseudoexfoliation syndrome (PXF) and healthy controls of Asian-Indian origin. Methods: In this cross-sectional study, 33 eyes of 33 PXF patients and 40 healthy eyes of 40 controls underwent OCT and OCT angiography (OCTA). Eyes with intraocular pressure (IOP) >21mmHg, glaucomatous disc changes, or any other ocular pathology were excluded. Peripapillary vessel density (VD) and retinal nerve fiber layer (RNFL) thickness were determined from the optic disc scans. Parafoveal VD and ganglion cell complex (GCC) thickness were measured from the macular scans. These parameters were compared between the groups using mixed effect models after adjusting for clinical confounders such as IOP, as well as SSI of the scans. Results: The 2 groups were demographically similar. Average RNFL (94µm vs 100µm, p = 0.01) and GCC (91µm vs 95µm, p = 0.03) were thinner in the PXF group compared to controls. The average peripapillary VD appeared lower in the PXF groups compared to controls (58.2% vs 58.8%, p = 0.04), but after adjusting for IOP and SSI, no difference was noted (p = 0.39). After accounting for confounders, parafoveal VD in the PXF group was significantly lower compared to controls (44.3% vs 46.8%, p = 0.008). Conclusion: Peripapillary RNFL thickness, parafoveal GCC thickness and parafoveal VD were decreased in eyes with PXF when compared to controls. VD measurements are associated with the SSI and, therefore, clinicians and researchers evaluating OCTA scans quantitatively must consider the SSI value during analysis and interpretation.

Outcomes of Deep Sclerectomy following Failed XEN Gel Stent Implantation in Open-Angle Glaucoma: A Prospective Study.

Background: The purpose of this study is to evaluate the outcome of deep sclerectomy (DS) as a secondary procedure following failed ab-interno XEN gel stent implantation in patients with open-angle glaucoma. Methods: Prospective, single-center, non-randomized, interventional study. Consecutive eyes that underwent mitomycin C (MMC) augmented XEN gel stent surgery, with uncontrolled intraocular pressure (IOP) or signs of disease progression, were included to undergo MMC-augmented DS. Primary efficacy outcome was surgical success, defined as complete when the unmedicated IOP was 12 mmHg or less, or 15 mmHg or less and 20% lower than at the timing of XEN failure and defined as qualified when the IOP fulfilled the same conditions with fewer medications than before deep sclerectomy. Secondary measures were mean reduction in IOP and in the number of medications, and the rates of complications. Results: Seventeen eyes were enrolled with a mean age of 72.1 ± 8.2 years (66.7% women). The mean follow-up was 20.1 ± 4.9 months, with more than 12-month data available from 15 eyes. Following DS, IOP decreased significantly from 22.6 ± 5.3 mmHg to 12.3 ± 5.5 (45.6%; p < 0.001). Antiglaucoma medications dropped from 1.1 ± 0.9 to 0.3 ± 0.7. Complete success was obtained in 40% of eyes using the threshold of 12 mmHg or less and a 20% decrease of IOP, and in 60% using the 15 mmHg or less threshold. Adverse events were observed in 20% of eyes (bleb leakage (13.3%); hypotony (6.7%)). No cases of choroidal detachment or hypotony maculopathy were reported. Conclusions: Failed XEN gel stent implantation does not seem to negatively affect the safety and efficacy of subsequent deep sclerectomy surgery.

Prevalence of primary angle-closure disease in retinitis pigmentosa.

Purpose: To determine the prevalence of primary angle-closure disease (PACD) in patients with retinitis pigmentosa (RP). Methods: This was a retrospective review of the electronic medical records of all RP patients over the age of 10 years attending the Genetics Eye Clinic of a tertiary-care hospital during a 7-year period. Information regarding age, gender, vision, refraction, lens, intraocular pressure (IOP), type of RP, and inheritance pattern using pedigree charts for all patients were obtained. Patients with a shallow anterior chamber, high IOP, or glaucomatous optic discs were referred to the glaucoma department where they underwent additional IOP measurements, a gonioscopy, and disc evaluation by a glaucoma specialist. The prevalence of PACD was determined. Results: A total of 618 RP patients were examined during the study period, of which 95.1% had typical RP. The prevalence of primary angle-closure suspects was 2.9%, primary angle closure was 0.65%, and primary angle-closure glaucoma (PACG) was 2.27%. In contrast, the prevalence of primary open-angle glaucoma was 1.29%. The prevalence of PACG in those older than 40 years was 3.8% (95% confidence interval: 1.6-6.0). Conclusion: The prevalence of PACG in RP patients over 40 years was higher than that found in the general population of a similar age (3.8% vs. 0.8%). In our cohort of RP patients, 5.9% had PACD. Hence, gonioscopy is warranted in all RP patients to identify this condition and treat it appropriately.

Point-wise variability of threshold sensitivity of 24-2 and 10-2 visual fields.

PURPOSE: To evaluate point-wise variability of threshold sensitivity at different test locations on 24-2 and 10-2 visual field (VF). MATERIALS AND METHODS: Electronic medical records of patients seen at a tertiary eye care center were screened to include those with at least 3 reliable VF with glaucomatous defects involving fixation on 24-2 and confirmed on 10-2 test strategy. Ninety eyes of 90 patients were categorized into 3 severity groups based on mean deviation (MD on 24-2) test strategy; MD<-6 dB and >-12 dB, <-12 dB and >-20 dB and <-20 dB and >-30 dB. Variability of threshold sensitivity at all topographical test locations in central (ring 1), mid-peripheral (ring 2), peripheral rings on 24-2 VF test strategy (ring 3), and central (ring 4) and paracentral (ring 5) on 10-2 VF test along with variability of visual field index and central field index were calculated by multilevel mixed effects model. RESULTS: Central ring1 on 24-2 and ring 4 on 10-2 showed higher variability (>10 dB) than peripheral ring 2, 3, and 5. Seventy-three eyes were adjudged as stable and 17 as progressing in this cohort. The average ring and point-wise variability was higher in stable eyes (2-6 dB) across all glaucoma severities. Across severity, variability was seen to decrease with increasing severity with minimal variability in point-wise threshold sensitivity beyond MD <-20 dB. CONCLUSION: Central test points/ring on 24-2 and 10-2 with greater threshold variability suggests that status of the eye, severity and topographical location of test points should be incorporated into conventional progression algorithms to predict true glaucoma progression.

Deep Learning for Glaucoma Detection and Identification of Novel Diagnostic Areas in Diverse Real-World Datasets.

Purpose: To develop a three-dimensional (3D) deep learning algorithm to detect glaucoma using spectral-domain optical coherence tomography (SD-OCT) optic nerve head (ONH) cube scans and validate its performance on ethnically diverse real-world datasets and on cropped ONH scans. Methods: In total, 2461 Cirrus SD-OCT ONH scans of 1012 eyes were obtained from the Glaucoma Clinic Imaging Database at the Byers Eye Institute, Stanford University, from March 2010 to December 2017. A 3D deep neural network was trained and tested on this unique raw OCT cube dataset to identify a multimodal definition of glaucoma excluding other concomitant retinal disease and optic neuropathies. A total of 1022 scans of 363 glaucomatous eyes (207 patients) and 542 scans of 291 normal eyes (167 patients) from Stanford were included in training, and 142 scans of 48 glaucomatous eyes (27 patients) and 61 scans of 39 normal eyes (23 patients) were included in the validation set. A total of 3371 scans (Cirrus SD-OCT) from four different countries were used for evaluation of the model: the non overlapping test dataset from Stanford (USA) consisted of 694 scans: 241 scans from 113 normal eyes of 66 patients and 453 scans of 157 glaucomatous eyes of 89 patients. The datasets from Hong Kong (total of 1625 scans; 666 OCT scans from 196 normal eyes of 99 patients and 959 scans of 277 glaucomatous eyes of 155 patients), India (total of 672 scans; 211 scans from 147 normal eyes of 98 patients and 461 scans from 171 glaucomatous eyes of 101 patients), and Nepal (total of 380 scans; 158 scans from 143 normal eyes of 89 patients and 222 scans from 174 glaucomatous eyes of 109 patients) were used for external evaluation. The performance of the model was then evaluated on manually cropped scans from Stanford using a new algorithm called DiagFind. The ONH region was cropped by identifying the appropriate zone of the image in the expected location relative to Bruch's Membrane Opening (BMO) using a commercially available imaging software. Subgroup analyses were performed in groups stratified by eyes, myopia severity of glaucoma, and on a set of glaucoma cases without field defects. Saliency maps were generated to highlight the areas the model used to make a prediction. The model's performance was compared to that of a glaucoma specialist using all available information on a subset of cases. Results: The 3D deep learning system achieved area under the curve (AUC) values of 0.91 (95% CI, 0.90-0.92), 0.80 (95% CI, 0.78-0.82), 0.94 (95% CI, 0.93-0.96), and 0.87 (95% CI, 0.85-0.90) on Stanford, Hong Kong, India, and Nepal datasets, respectively, to detect perimetric glaucoma and AUC values of 0.99 (95% CI, 0.97-1.00), 0.96 (95% CI, 0.93-1.00), and 0.92 (95% CI, 0.89-0.95) on severe, moderate, and mild myopia cases, respectively, and an AUC of 0.77 on cropped scans. The model achieved an AUC value of 0.92 (95% CI, 0.90-0.93) versus that of the human grader with an AUC value of 0.91 on the same subset of scans (\(P=0.99\)). The performance of the model in terms of recall on glaucoma cases without field defects was found to be 0.76 (0.68-0.85). Saliency maps highlighted the lamina cribrosa in glaucomatous eyes versus superficial retina in normal eyes as the regions associated with classification. Conclusions: A 3D convolutional neural network (CNN) trained on SD-OCT ONH cubes can distinguish glaucoma from normal cases in diverse datasets obtained from four different countries. The model trained on additional random cropping data augmentation performed reasonably on manually cropped scans, indicating the importance of lamina cribrosa in glaucoma detection. Translational Relevance: A 3D CNN trained on SD-OCT ONH cubes was developed to detect glaucoma in diverse datasets obtained from four different countries and on cropped scans. The model identified lamina cribrosa as the region associated with glaucoma detection.

Rates of Choroidal Microvasculature Dropout and Retinal Nerve Fiber Layer Changes in Glaucoma.

PURPOSE: To evaluate the association between rates of choroidal microvasculature dropout (MvD) change and rates of circumpapillary retinal nerve fiber layer (cpRNFL) loss in primary open-angle glaucoma (POAG) eyes. DESIGN: Cohort study from clinical trial data. METHODS: A total of 91 eyes of 68 POAG patients with and without localized MvD at baseline with at least 4 visits and 2 years of follow-up with optical coherence tomography angiography (OCT-A) and OCT scans were included. Area and angular circumference of MvD were evaluated on OCT-A en face and B-scan choroidal vessel density images during the follow-up period. Joint longitudinal mixed effects models were used to estimate the rates of change in MvD area or angular circumference and RNFL thickness. Univariable and multivariable regressions were completed to identify the factors contributing to cpRNFL thinning. RESULTS: MvD was identified in 53 eyes (58.2%) at baseline. Seventeen eyes (18.6%) that did not show MvD at baseline developed it over the follow-up period. Over a mean follow-up of 4.0 years, the mean rates of change in MvD area and angular circumference (95% CI) were 0.05 (0.04, 0.06) mm2 per year and 13.2° (10.7°, 15.8°) per year, respectively. In multivariable models, the rate of cpRNFL thinning was significantly associated with the rates of change in MvD area and angular circumference (P = .008 and P = .009, respectively). CONCLUSIONS: Rates of MvD area and angular circumference change over time were associated with concurrent rates of cpRNFL loss in POAG eyes.

A novel cyclopentyl methyl ether electrolyte solvent with a unique solvation structure for subzero (-40 °C) lithium-ion batteries.

1 M LiFSI in cyclopentyl methyl ether is shown as a novel electrolyte with a unique solvation structure to form a thin robust multilayer solid electrolyte interface with an inorganic LiF-rich inner layer. Aggregates and contact ion pairs are actively formed in the solvation shell and reduced on the graphite anode during lithiation. This EC-free electrolyte provides 86.9% initial efficiency, and 355 mA h g-1 over 350 cycles with an excellent capacity retention of 84% at a 1C rate. An excellent low-temperature performance of 370, 337, and 330 mA h g-1 at 0, -10, and -20 °C, respectively, at a 0.1C rate is recorded. Furthermore, at -40 °C, the graphite half-cell has a capacity of 274 mA h g-1 without electrolyte freezing.

Upregulated NOTCH Signaling in the Lens of Patients With Pseudoexfoliation Syndrome Compared With Pseudoexfoliation Glaucoma Suggests Protective Role.

PRCIS: NOTCH signaling is significantly upregulated in the lens capsules of eyes with pseudoexfoliation syndrome (PXF) but not in those with pseudoexfoliation glaucoma (PXG) when compared with healthy controls. PURPOSE: NOTCH signaling has neuroprotective functions and altered NOTCH signaling is associated with neurodegenerative diseases with protein aggregation such as Alzheimer disease. As PXG is also a protein aggregate disease associated with neural degeneration, NOTCH molecular expression was explored in the lens capsules of patients with PXF, PXG, primary open-angle glaucoma (POAG), and healthy controls. METHODS: Anterior lens capsules were collected from 106 patients (27 PXF, 24 PXG, 22 POAG, and 33 controls) undergoing cataract surgery. Gene expression profiling for NOTCH pathway molecules (ligands, receptors, and downstream target genes) was performed on the tissue using a quantitative reverse transcription-polymerase chain reaction. The results were confirmed by protein analysis using dot-blot or immunostaining techniques. RESULTS: There was no difference in the demographic characteristics between the groups. There was an increase in NOTCH4 receptor expression (>14-fold) in the PXF group as compared with the controls. Similarly, the Delta-like 3 and Delta-like 4 ligands were significantly elevated in the PXF group compared with controls (P<0.05). Downstream targets HES3, HES5, and HEY1 expression were significantly elevated (P<0.005) in PXF lens capsules, confirming a higher activity of NOTCH signaling in this cohort. Immunostaining also corroborated the gene expression profile. CONCLUSION: The finding that NOTCH signaling is significantly upregulated in the lens capsule of eyes with PXF and not in PXG or POAG patients suggests a possible protective role in the development of glaucoma.

Long-term outcomes and risk factors for failure of glaucoma filtering surgery in eyes with vernal keratoconjunctivitis and steroid-induced glaucoma.

PURPOSE: To report outcomes and assess the risk factors for failure of trabeculectomy (trab), trabeculectomy with mitomycin-C (trabMMC), and combined trabeculectomy with cataract extraction (CT) in vernal keratoconjunctivitis (VKC) eyes with steroid-induced glaucoma (SIG). METHODS: Trab was performed in 45 eyes of 30 subjects, trabMMC in 36 eyes of 25 subjects, and CT in 34 eyes of 27 subjects. Success was complete when intraocular pressure (IOP) was between 6 and 21 mm Hg without anti-glaucoma medications (AGM) and qualified with AGM. RESULTS: Median age (14 vs. 16.3 and 17.4 years) was significantly less in the trab cohort (P = 0.007). Majority (88%-93%) were male (P = 0.78). Preoperatively, median duration of steroid usage was >2 years (P = 0.52), mean IOP (32, 29.4, and 28.4; P = 0.26) and median cup:disc ratio (CDR) (0.9; P = 0.27) were similar in the three groups. Complete success (76%, 71%, and 66% at 5 years; P = 0.91), and qualified success (88%, 97%, and 94% at 5 years; P = 1.0) with trab, trabMMC, and CT, respectively, were similar. Preoperative factors significantly associated with qualified failure (multiple logistic regression) were older children, longer duration of VKC, longer duration and mixed type of steroid use (all P < 0.001) and larger CDR (P < 0.02). At the last follow-up, 38% in trab, 33% in trabMMC, and 50% eyes in CT were blind (visual acuity ≤20/400 and/or visual field ≤10°) due to glaucoma (P = 0.33). CONCLUSION: The surgical success for all three types of surgery was similar at 5-years. Chronic VKC and long-term steroid use were associated with surgical failure. The majority had advanced disease and a significant proportion were blind due to glaucoma.