Omidenepag Isopropyl 0.002% versus Latanoprost 0.005% in Open-Angle Glaucoma/Ocular Hypertension: The Randomized Phase III PEONY Trial.

Purpose: To compare the efficacy and safety of omidenepag isopropyl (OMDI) 0.002% with latanoprost 0.005% once daily in Asian subjects with open-angle glaucoma (OAG)/ocular hypertension (OHT). Methods: In this Phase III randomized, observer-masked, active-controlled, multinational trial (NCT02981446), subjects aged ≥18 years with OAG/OHT in both eyes and baseline intraocular pressure (IOP) ≥22 mmHg and ≤34 mmHg were randomized 1:1 to OMDI or latanoprost. IOP was measured at 9AM, 1PM, and 5PM at baseline, 1 week, 6 weeks, and 3 months. Adverse events (AEs) were recorded. Non-inferiority of OMDI to latanoprost was tested for primary and key secondary endpoints. Results: Each group included 185 subjects. Mean diurnal IOP from baseline to month 3 was reduced 7.1 mmHg (28.8%) with OMDI and 7.8 mmHg (31.3%) with latanoprost, with the least-squares mean difference (OMDI minus latanoprost) being 0.6 mmHg (95% CI: 0.0, 1.2 mmHg; p = 0.0366), indicating non-inferiority. Mean IOP reductions at the nine timepoints were -5.8 to -7.3 mmHg (23.5-29.5%) for OMDI and -6.1 to -7.9 mmHg (24.3-31.7%) for latanoprost. Non-inferiority per FDA criteria was also met. Rates of all AEs, ocular AEs, and ocular AEs associated with treatment were 40.0%, 36.8%, and 23.2%, respectively, for OMDI and 29.7%, 21.1%, and 11.9%, respectively, for latanoprost. Conjunctival hyperemia rates were higher with OMDI than latanoprost (11.9% vs 5.4%). Most AEs were mild, with no serious ocular AEs. Conclusion: OMDI safely and effectively reduces IOP in Asian subjects with OAG/OHT, with mean diurnal IOP at Month 3 and per-timepoint IOP reductions non-inferior to those of latanoprost.

PEONY Study: Testing How Well and How Safely Omidenepag Isopropyl Eye Drops Treat People with Glaucoma or Ocular Hypertension Compared with Latanoprost. Who took part in the study? Three hundred and seventy participants average age of 57 years, from 34 centers across four Asian countries who had glaucoma or high pressure in both eyes were randomly divided into two groups. One group (185 people; 50%) was given OMDI, and the other group (185 people; 50%) latanoprost for 3 months. The intraocular pressure of both eyes was measured in all participants at three time points (9 AM, 1 PM, and 5 PM) after 1 week, 6 weeks, and 3 months of treatment. The primary endpoint was the average of the daily eye pressure after 3 months of treatment. The safety of OMDI was also assessed. Study results. After 3 months of treatment, OMDI decreased the eye pressure by 29%. This was similar to latanoprost, which decreased the eye pressure by 31% over the same time period. OMDI was safe and well tolerated by those participants who received it. The most common side-effect in people receiving OMDI or latanoprost was conjunctival hyperemia (red eye) (experienced by 22 people receiving OMDI, and 10 people receiving latanoprost). Conclusions After 3 months of use, OMDI was found to safely reduce high eye pressure to a similar level as latanoprost in Asian people with glaucoma or high eye pressure.

Clinical Staging of Prostaglandin-Associated Periorbitopathy Syndrome in Glaucoma: A Review from Asia.

PURPOSE: Topical prostaglandin analogues are commonly used to treat patients with glaucoma, but may cause periocular and periorbital complications known as prostaglandin-associated periorbitopathy syndrome (PAPS). METHODS: A literature review was conducted on PAPS. Given the lack of consensus on grading PAPS, glaucoma specialists from Asia convened to evaluate current PAPS grading systems and propose additional considerations in grading PAPS. RESULTS: Existing grading systems are limited by the lack of specificity in defining grades and consideration for patients' subjective perception of symptoms. Patient-reported symptoms (e.g., via a self-assessment tool) and additional clinical assessments (e.g., exophthalmometry, lid laxity, differences between tonometry results, baseline measurements, and external ocular photographs) would be beneficial for grading PAPS systematically. CONCLUSIONS: Effective management of PAPS could be facilitated by a common clinical grading system to consistently and accurately diagnose and characterise symptoms. Further research is required to validate specific recommendations and approaches to stage and monitor PAPS.

Comparison of intraocular pressure and anterior segment parameters in subjects with asymmetrical primary angle closure disease.

BACKGROUND: To compare intraocular pressure (IOP) and anterior segment parameters between eyes with unilateral primary angle closure glaucoma (PACG) and their fellow eyes with primary angle closure (PAC) or primary angle closure suspect (PACS). METHODS: Subjects underwent anterior segment imaging using 360-degree swept-source optical coherence tomography (SS-OCT, CASIA Tomey, Nagoya, Japan) and ocular investigations including gonioscopy and IOP measurement. Each SS-OCT scan (divided into 8 frames, 22.5 degrees apart) was analysed and an average was obtained for the following anterior segment parameters: iridotrabecular contact (ITC), angle opening distance (AOD750), iris thickness and curvature, anterior chamber width, depth and area (ACW, ACD and ACA) and lens vault (LV). RESULTS: Among 132 unilateral PACG subjects (mean age: 62.91 ± 7.2 years; 59.1% male), eyes with PACG had significantly higher presenting IOP (24.81 ± 0.94 vs. 18.43 ± 0.57 mmHg, p < 0.001), smaller gonioscopic Shaffer grade (2.07 ± 0.07 vs. 2.31 ± 0.07, p < 0.001) and a greater extent of peripheral anterior synechiae (PAS, 1.21 ± 0.21 vs. 0.54 ± 0.16 clock hours, p = 0.001). PACG eyes also exhibited increased ITC, ITC area, greater LV and smaller AOD750, ACD and ACA (all p < 0.05). Using the forward stepwise regression model, an increase in 1 mmHg in presenting IOP before laser peripheral iridotomy (LPI) increases the odds of having PACG by 9% (95% confidence interval 5%-14%). CONCLUSIONS: PACG eyes have higher presenting IOP, smaller anterior segment parameters, greater extent of PAS, and larger LV compared to their fellow eyes with angle closure. Narrower anterior chamber dimensions and higher presenting IOP before LPI may increase risk of chronic elevated IOP and glaucomatous optic neuropathy after LPI.

Biomarkers for prognosis of meningioma patients: A systematic review and meta-analysis.

Meningioma is the most common primary brain tumor and many studies have evaluated numerous biomarkers for their prognostic value, often with inconsistent results. Currently, no reliable biomarkers are available to predict the survival, recurrence, and progression of meningioma patients in clinical practice. This study aims to evaluate the prognostic value of immunohistochemistry-based (IHC) biomarkers of meningioma patients. A systematic literature search was conducted up to November 2023 on PubMed, CENTRAL, CINAHL Plus, and Scopus databases. Two authors independently reviewed the identified relevant studies, extracted data, and assessed the risk of bias of the studies included. Meta-analyses were performed with the hazard ratio (HR) and 95% confidence interval (CI) of overall survival (OS), recurrence-free survival (RFS), and progression-free survival (PFS). The risk of bias in the included studies was evaluated using the Quality in Prognosis Studies (QUIPS) tool. A total of 100 studies with 16,745 patients were included in this review. As the promising markers to predict OS of meningioma patients, Ki-67/MIB-1 (HR = 1.03, 95%CI 1.02 to 1.05) was identified to associate with poor prognosis of the patients. Overexpression of cyclin A (HR = 4.91, 95%CI 1.38 to 17.44), topoisomerase II α (TOP2A) (HR = 4.90, 95%CI 2.96 to 8.12), p53 (HR = 2.40, 95%CI 1.73 to 3.34), vascular endothelial growth factor (VEGF) (HR = 1.61, 95%CI 1.36 to 1.90), and Ki-67 (HR = 1.33, 95%CI 1.21 to 1.46), were identified also as unfavorable prognostic biomarkers for poor RFS of meningioma patients. Conversely, positive progesterone receptor (PR) and p21 staining were associated with longer RFS and are considered biomarkers of favorable prognosis of meningioma patients (HR = 0.60, 95% CI 0.41 to 0.88 and HR = 1.89, 95%CI 1.11 to 3.20). Additionally, high expression of Ki-67 was identified as a prognosis biomarker for poor PFS of meningioma patients (HR = 1.02, 95%CI 1.00 to 1.04). Although only in single studies, KPNA2, CDK6, Cox-2, MCM7 and PCNA are proposed as additional markers with high expression that are related with poor prognosis of meningioma patients. In conclusion, the results of the meta-analysis demonstrated that PR, cyclin A, TOP2A, p21, p53, VEGF and Ki-67 are either positively or negatively associated with survival of meningioma patients and might be useful biomarkers to assess the prognosis.

Impact of peripheral anterior synechiae on the outcome of combined phacoemulsification, goniosynechialysis and goniotomy for primary angle-closure glaucoma and cataract: a multicenter observational study.

PURPOSE: To evaluate the impact of the extent of peripheral anterior synechiae (PAS) on the effectiveness and safety of combined phacoemulsification (PEI), goniosynechialysis (GSL), and goniotomy (GT) in eyes with primary angle-closure glaucoma (PACG) and cataract. PATIENTS AND METHODS: This study included patients diagnosed with PACG and cataract who underwent combined PEI and 120 degrees GSL plus GT (PEI+GSL+GT) between April 2020 and October 2022 at 10 ophthalmic institutes. Eligible patients were divided into three groups based on the extent of PAS: 180°≤PAS<270°, 270°≤PAS<360°, and PAS=360°. Data on intraocular pressure (IOP), the number of ocular hypotensive medications, and complications were collected and compared. The study defined complete success as postoperative IOP within the 6-18 mmHg range and a 20% reduction from baseline without the use of topical medications. Qualified success was defined in the same way as complete success, but it allowed for the use of ocular hypotensive medications. RESULTS: Three hundred and four eyes of 283 patients were included. The mean follow-up was 12.50±1.24 months. All groups experienced a significant reduction in IOP after the surgery (P <0.05). There were no significant differences in final IOP, number of medications, and cumulative complete and qualified success rates among the three groups (P >0.05). The groups with 270°≤PAS<360°had a higher frequency of hyphema compared to 180°≤PAS<270° (P = 0.044). CONCLUSIONS: PEI+GSL+GT has proven to be an effective treatment for PACG with cataract over one year period. However, the outcome was not correlated with preoperative extent of PAS. PRCIS: The combination of phacoemulsification, goniosynechialysis and goniotomy is an effective treatment for primary angle-closure glaucoma patients with cataract, and this is not linked to the extent of preoperative peripheral anterior synechiae.

Retinal Nerve Fiber Layer Damage Assessment in Glaucomatous Eyes Using Retinal Retardance Measured by Polarization-Sensitive Optical Coherence Tomography.

Purpose: To assess the diagnostic performance and structure-function association of retinal retardance (RR), a customized metric measured by a prototype polarization-sensitive optical coherence tomography (PS-OCT), across various stages of glaucoma. Methods: This cross-sectional pilot study analyzed 170 eyes from 49 healthy individuals and 68 patients with glaucoma. The patients underwent PS-OCT imaging and conventional spectral-domain optical coherence tomography (SD-OCT), as well as visual field (VF) tests. Parameters including RR and retinal nerve fiber layer thickness (RNFLT) were extracted from identical circumpapillary regions of the fundus. Glaucomatous eyes were categorized into early, moderate, or severe stages based on VF mean deviation (MD). The diagnostic performance of RR and RNFLT in discriminating glaucoma from controls was assessed using receiver operating characteristic (ROC) curves. Correlations among VF-MD, RR, and RNFLT were evaluated and compared within different groups of disease severity. Results: The diagnostic performance of both RR and RNFLT was comparable for glaucoma detection (RR AUC = 0.98, RNFLT AUC = 0.97; P = 0.553). RR showed better structure-function association with VF-MD than RNFLT (RR VF-MD = 0.68, RNFLT VF-MD = 0.58; z = 1.99; P = 0.047) in glaucoma cases, especially in severe glaucoma, where the correlation between VF-MD and RR (r = 0.73) was significantly stronger than with RNFLT (r = 0.43, z = 1.96, P = 0.050). In eyes with early and moderate glaucoma, the structure-function association was similar when using RNFLT and RR. Conclusions: RR and RNFLT have similar performance in glaucoma diagnosis. However, in patients with glaucoma especially severe glaucoma, RR showed a stronger correlation with VF test results. Further research is needed to validate RR as an indicator for severe glaucoma evaluation and to explore the benefits of using PS-OCT in clinical practice. Translational Relevance: We demonstrated that PS-OCT has the potential to evaluate the status of RNFL structural damage in eyes with severe glaucoma, which is currently challenging in clinics.

Efficacy and Safety of Surgical Peripheral Iridectomy, Goniosynechialysis, and Goniotomy for Advanced Primary Angle-closure Glaucoma without Cataract: One-year Results of a Multicenter Study.

PRCIS: The combination of surgical peripheral iridectomy, goniosynechialysis, and goniotomy is a safe and effective surgical approach for advanced primary angle-closure glaucoma without cataract. PURPOSE: To evaluate the efficacy and safety of surgical peripheral iridectomy (SPI), goniosynechialysis (GSL), and goniotomy (GT) in advanced primary angle-closure glaucoma (PACG) eyes without cataract. PATIENTS AND METHODS: A prospective multicenter observational study was performed for patients who underwent combined SPI, GSL, and GT for advanced PACG without cataract. Patients were assessed before and after the operation. Complete success was defined as achieving intraocular pressure (IOP) between 6-18 mm Hg with at least a 20% reduction compared to baseline, without the use of ocular hypotensive medications or reoperation. Qualified success adopted the same criteria but allowed medication use. Factors associated with surgical success were analyzed using logistic regression. RESULTS: A total of 61 eyes of 50 advanced PACG were included. All participants completed 12 months of follow-up. Thirty-six eyes (59.0%) achieved complete success, and 56 eyes (91.8%) achieved qualified success. Preoperative and postsurgical at 12 months mean IOPs were 29.7±7.7 and 16.1±4.8 mm Hg, respectively. The average number of ocular hypotensive medications decreased from 1.9 to 0.9 over 12 months. The primary complications included IOP spike (n=9), hyphema (n=7), and shallow anterior chamber (n=3). Regression analysis indicated that older age (odds ratio [OR]=1.09; P=0.043) was positively associated with complete success, while a mixed angle closure mechanism (OR=0.17; P=0.036) reduced success rate. CONCLUSIONS: The combination of SPI, GSL, and GT is a safe and effective surgical approach for advanced PACG without cataract. It has great potential as a first-line treatment option for these patients.

Enhancing the structure-function relationship in glaucoma using anatomical compensation of retinal nerve fibre layer.

BACKGROUND/AIMS: To investigate whether compensating retinal nerve fibre layer (RNFL) thickness measurements for demographic and anatomical ocular factors can strengthen the structure-function relationship in patients with glaucoma. METHODS: 600 eyes from 412 patients with glaucoma (mean deviation of the visual field (MD VF) -6.53±5.55 dB) were included in this cross-sectional study. Participants underwent standard automated perimetry and spectral-domain optical coherence tomography imaging (Cirrus; Carl Zeiss Meditec). Compensated RNFL thickness was computed considering age, refractive error, optic disc parameters and retinal vessel density. The relationship between MD VF and RNFL thickness measurements, with or without demographic and anatomical compensation, was evaluated sectorally and focally. RESULTS: The superior arcuate sector exhibited the highest correlation between measured RNFL and MD VF, with a correlation of 0.49 (95% CI 0.37 to 0.59). Applying the compensated RNFL data increased the correlation substantially to 0.62 (95% CI 0.52 to 0.70; p<0.001). Only 61% of the VF locations showed a significant relationship (Spearman's correlation of at least 0.30) between structural and functional aspects using measured RNFL data, and this increased to 78% with compensated RNFL measurements. In the 10°-20° VF region, the slope below the breakpoint for compensated RNFL thickness demonstrated a more robust correlation (slope=1.66±0.18 µm/dB; p<0.001) than measured RNFL (slope=0.27±0.67 µm/dB; p=0.688). CONCLUSION: Compensated RNFL data improve the correlation between RNFL measurements and VF parameters. This indicates that creating structure-to-function maps that consider anatomical variances may aid in identifying localised structural and functional loss in glaucoma.

CRISPR-Cas9-mediated deletion of carbonic anhydrase 2 in the ciliary body to treat glaucoma.

The carbonic anhydrase 2 (Car2) gene encodes the primary isoenzyme responsible for aqueous humor (AH) production and plays a major role in the regulation of intraocular pressure (IOP). The CRISPR-Cas9 system, based on the ShH10 adenovirus-associated virus, can efficiently disrupt the Car2 gene in the ciliary body. With a single intravitreal injection, Car2 knockout can significantly and sustainably reduce IOP in both normal mice and glaucoma models by inhibiting AH production. Furthermore, it effectively delays and even halts glaucomatous damage induced by prolonged high IOP in a chronic ocular hypertension model, surpassing the efficacy of clinically available carbonic anhydrase inhibitors such as brinzolamide. The clinical application of CRISPR-Cas9 based disruption of Car2 is an attractive therapeutic strategy that could bring additional benefits to patients with glaucoma.

Replacing the postoperative week 1 visit after routine phacoemulsification with a telephone consult.

OBJECTIVE: To assess the safety of replacing the postoperative week 1 (POW1) clinic visit with a nurse-conducted telephone call. DESIGN: Retrospective observational study that included cases from January 2019 to June 2021. PARTICIPANTS: Patients who had undergone uncomplicated phacoemulsification surgery with an unremarkable postoperative day 1 (POD1) examination. METHODS: All patients were seen in clinic on POD1 by an ophthalmologist. They then had a telephone conversation with a nurse at POW1 and subsequently an in-person postoperative month 1 (POM1) clinic consultation with an ophthalmologist. Main outcome measure was the incidence of unexpected management changes related to cataract surgery within POM1. Data also were collected on the reasons for unscheduled patient-initiated visits, additional procedures or medications, and postoperative visual acuity worse than 6/12 at POM1. RESULTS: Of the 20,475 patients, 541 patients (2.64%) had an unexpected management change within POM1. There were 565 patients (2.76%) who had self-initiated unscheduled visits between POD1 to POM1. There were 23 patients (0.11%) who required additional surgery within POM1 and 1 patient (0.005%) with endophthalmitis. The most common indication for additional surgical procedures was retained lens material (7 patients, 30.43%). Visual acuity was worse than 6/12 in 1,199 patients (6.22%), with the most common causes attributed to preexisting ocular conditions. CONCLUSIONS: These results suggest that replacing the POW1 visit with a nurse-conducted telephone consult for patients who have undergone uncomplicated phacoemulsification surgery and had a normal POD1 consultation is safe.

Evaluation of changes of anterior segment parameters in patients with pseudoexfoliation syndrome after cataract surgery using anterior segment optical coherence tomography.

The aim of the study was to compare the anterior segment parameters after cataract surgery in pseudoexfoliation syndrome (PEX) and control eyes. We conducted a prospective comparative study of 36 eyes (PEX group), 16 eyes (PEXG group) and 46 eyes (control group) of 98 patients after phacoemulsification with intraocular lens implantation. Before surgery, 1 week, 1 month and 3 months postoperatively, anterior chamber parameters were evaluated by swept source anterior segment optical coherence tomography (AS-OCT). Anterior chamber depth (ACD), angle opening distance (AOD500/750), trabecular-iris space area (TISA500/750), trabecular-iris angle (TIA500/750) and lens vault (LV) were assessed at each study visit. Preoperatively, ACD, AOD500/750 and TISA500/750 were significantly smaller, while LV was significantly greater in PEX and PEXG eyes than in controls. 3 months postoperatively all irido-corneal parameters and ACD were significantly greater in all study groups without intergroup differences. ACD and LV significantly increased in PEX group between 1 and 3 months after surgery while being stable in control group. Relative increases in ACD, AOD500, TISA750, TIA500/750 were significantly higher in PEX and PEXG groups than in controls. Our study finds that ACD and iridocorneal parameters in AS-OCT demonstrated significantly greater relative increases 3 months after phacoemulsification in PEX and PEXG groups than in control eyes. Significantly greater deepening of anterior chamber and opening of the irido-corneal angle may be a reason for different refractive outcomes and IOP control in patients with PEX and PEXG after routine cataract surgery.

Diagnostic criteria of anterior segment swept-source optical coherence tomography to detect gonioscopic angle closure.

AIMS: To compare the diagnostic performance of 360° anterior segment optical coherence tomography assessment by applying normative percentile cut-offs versus iris trabecular contact (ITC) for detecting gonioscopic angle closure. METHODS: In this multicentre study, 394 healthy individuals were included in the normative dataset to derive the age-specific and angle location-specific normative percentiles of angle open distance (AOD500) and trabecular iris space area (TISA500) which were measured every 10° for 360°. 119 healthy participants and 170 patients with angle closure by gonioscopy were included in the test dataset to investigate the diagnostic performance of three sets of criteria for detection of gonioscopic angle closure: (1) the 10th and (2) the 5th percentiles of AOD500/TISA500, and (3) ITC (ie, AOD500/TISA500=0 mm/mm2). The number of angle locations with angle closure defined by each set of the criteria for each eye was used to generate the receiver operating characteristic (ROC) curve for the discrimination between gonioscopic angle closure and open angle. RESULTS: Of the three sets of diagnostic criteria examined, the area under the ROC curve was greatest for the 10th percentile of AOD500 (0.933), whereas the ITC criterion AOD500=0 mm showed the smallest area under the ROC (0.852) and the difference was statistically significant with or without adjusting for age and axial length (p<0.001). The criterion ≥90° of AOD500 below the 10th percentile attained the best sensitivity 87.6% and specificity 84.9% combination for detecting gonioscopic angle closure. CONCLUSIONS: Applying the normative percentiles of angle measurements yielded a higher diagnostic performance than ITC for detecting angle closure on gonioscopy.

Phacogoniotomy versus phacotrabeculectomy for advanced primary angle-closure glaucoma with cataract: A randomized non-inferiority trial.

PURPOSE: To investigate the effectiveness and safety of phacogoniotomy versus phacotrabeculectomy (PVP) among patients with advanced primary angle-closure glaucoma (PACG) and cataracts. DESIGN: Multicenter, randomized controlled, non-inferiority trial. METHODS: A total of 124 patients (124 eyes) with advanced PACG and cataracts were enrolled, with 65 in the phacogoniotomy group and 59 in the phacotrabeculectomy group. Patients were followed up for 12 months with standardized evaluations. The primary outcome was the reduction in intraocular pressure (IOP) from baseline to 12 months postoperatively, of which a non-inferiority margin of 4 mmHg was evaluated. Secondary outcomes included the cumulative surgical success rate, postoperative complications, and changes in the number of glaucoma medications. RESULTS: After 12 months, phacogoniotomy demonstrated non-inferiority to phacotrabeculectomy in terms of IOP reduction, with mean IOP reductions of - 26.1 mmHg and - 25.7 mmHg (P = 0.383), respectively, from baseline values of around 40 mmHg. Both groups experienced a significant reduction in the mean number of medications used postoperatively (P < 0.001). The cumulative success rate was comparable between the groups (P = 0.890). However, phacogoniotomy had a lower rate of postoperative complications and interventions (12.3% and 4.6%) compared to phacotrabeculectomy (23.7% and 20.3% respectively). The phacogoniotomy group reported shorter surgery time (22.1 ± 6.5 vs. 38.8 ± 11.1 min; P = 0.030) and higher quality of life (EQ-5D-5 L) improvement at 12 months (7.0 ± 11.5 vs. 3.0 ± 12.9, P = 0.010) than the phacotrabeculectomy group. CONCLUSIONS: Phacogoniotomy was non-inferior to phacotrabeculectomy in terms of IOP reduction for advanced PACG and cataracts. Additionally, phacogoniotomy provided a shorter surgical time, lower postoperative complication rate, fewer postoperative interventions, and better postoperative quality of life.

Serum CCDC25 Levels as a Potential Marker for Metabolic Syndrome.

BACKGROUND/AIM: Metabolic syndrome (MetS) stands as a significant risk for developing various severe health problems. Therefore, the discovery of biomarkers capable of predicting the progression of metabolic conditions is crucial for improving overall health outcomes. Recently, we reported that coiled-coil domain containing 25 (CCDC25) might be associated with key proteins involved in metabolic pathways, by bioinformatics analysis. Thus, we assumed that serum CCDC25 levels might have an association with MetS status. PATIENTS AND METHODS: In this study, based on the modified National Cholesterol Education Program-Adult Treatment Panel III (modified NCEP-ATP III) criteria, the participants who had three or more of abnormal criteria were defined as MetS, and those who had 1 or 2 abnormal criteria as pre-MetS groups; those who had no abnormal criteria were classified as the healthy control (HC) group. Serum CCDC25 levels were measured using the dot blot assay. RESULTS: The results showed that serum CCDC25 levels of the MetS group (0.072±0.026 ng/µl) were significantly higher (p<0.001) than that of pre-MetS (0.031±0.011 ng/µl) or HC groups (0.018±0.007 ng/µl). We can discern a consistent trend indicating that serum CCDC25 level is well correlated with the number of abnormal criteria of MetS of each participant. Although serum CCDC25 levels correlated with the distribution of all 5 MetS criteria, the highest correlation was seen in serum CCDC25 levels and triglyceride (TG) levels, with r=0.563, followed by systolic blood pressure (SBP) levels (r=0.557) and high-density lipoprotein-cholesterol (HDL-C) levels (r=-0.545). CONCLUSION: CCDC25 showed correlations with all MetS parameters, particularly with TG, SBP, and HDL-C. This prompts speculation that heightened CCDC25 levels may indicate the development and/or progression of those MetS-associated diseases.

Efficiency, Precision, Validity, and Reliability of GlauCAT-Asian Computerized Adaptive Tests in Measuring Glaucoma-Related Quality of Life.

Purpose: To determine the efficiency, precision, and agreement of GlauCAT-Asian and its corresponding validity and reliability. Methods: In this cross-sectional study, 219 participants (mean ± standard deviation age, 66.59 ± 8.61 years; 34% female) across the spectrum of glaucoma severity and 50 glaucoma suspects were recruited from glaucoma clinics in Singapore. Participants answered seven computerized adaptive testing (CAT) evaluations (Ocular Comfort, Activity Limitation, Lighting, Mobility, Concerns, Psychosocial, Glaucoma Management) and underwent eye examinations. Efficiency (mean number of items required for each CAT and time taken for CAT versus full item banks [IBs]), agreement (concordance between CATs and full IB person measures, henceforth referred to as scores), and precision (standard error of measurement [SE]) were evaluated. Other validity and reliability metrics were also assessed. Results: The mean number of items administered ranged from 9 (Mobility/Glaucoma Management) to 12 (Ocular Comfort). Compared to answering the full IBs, CATs provided an average time saving of 38.3% (range, 10% to 70.6% for Lighting and Activity Limitation, respectively). Agreement between scores obtained by CAT versus full IB was high (intracorrelation coefficient ≥0.75), as was precision of score estimates (mean SE range: 0.35 for Psychosocial to 0.29 for Mobility). Scores from Activity Limitation, Mobility, Lighting, and Concerns decreased significantly as glaucoma severity increased (criterion validity; P-trend <0.05). All tests displayed good convergent/divergent validity and test-retest reliability. Conclusions: GlauCAT-Asian provides efficient, precise, accurate, valid, and reliable measurement of the patient-centered impact of glaucoma. Translational Relevance: GlauCAT-Asian may provide a valuable clinical tool for ophthalmologists to monitor impact of disease progression and the effectiveness of therapies.

A multi-cohort genome-wide association study in African ancestry individuals reveals risk loci for primary open-angle glaucoma.

Primary open-angle glaucoma (POAG), the leading cause of irreversible blindness worldwide, disproportionately affects individuals of African ancestry. We conducted a genome-wide association study (GWAS) for POAG in 11,275 individuals of African ancestry (6,003 cases; 5,272 controls). We detected 46 risk loci associated with POAG at genome-wide significance. Replication and post-GWAS analyses, including functionally informed fine-mapping, multiple trait co-localization, and in silico validation, implicated two previously undescribed variants (rs1666698 mapping to DBF4P2; rs34957764 mapping to ROCK1P1) and one previously associated variant (rs11824032 mapping to ARHGEF12) as likely causal. For individuals of African ancestry, a polygenic risk score (PRS) for POAG from our mega-analysis (African ancestry individuals) outperformed a PRS from summary statistics of a much larger GWAS derived from European ancestry individuals. This study quantifies the genetic architecture similarities and differences between African and non-African ancestry populations for this blinding disease.

AI-based clinical assessment of optic nerve head robustness superseding biomechanical testing.

BACKGROUND/AIMS: To use artificial intelligence (AI) to: (1) exploit biomechanical knowledge of the optic nerve head (ONH) from a relatively large population; (2) assess ONH robustness (ie, sensitivity of the ONH to changes in intraocular pressure (IOP)) from a single optical coherence tomography (OCT) volume scan of the ONH without the need for biomechanical testing and (3) identify what critical three-dimensional (3D) structural features dictate ONH robustness. METHODS: 316 subjects had their ONHs imaged with OCT before and after acute IOP elevation through ophthalmo-dynamometry. IOP-induced lamina cribrosa (LC) deformations were then mapped in 3D and used to classify ONHs. Those with an average effective LC strain superior to 4% were considered fragile, while those with a strain inferior to 4% robust. Learning from these data, we compared three AI algorithms to predict ONH robustness strictly from a baseline (undeformed) OCT volume: (1) a random forest classifier; (2) an autoencoder and (3) a dynamic graph convolutional neural network (DGCNN). The latter algorithm also allowed us to identify what critical 3D structural features make a given ONH robust. RESULTS: All three methods were able to predict ONH robustness from a single OCT volume scan alone and without the need to perform biomechanical testing. The DGCNN (area under the curve (AUC): 0.76±0.08) outperformed the autoencoder (AUC: 0.72±0.09) and the random forest classifier (AUC: 0.69±0.05). Interestingly, to assess ONH robustness, the DGCNN mainly used information from the scleral canal and the LC insertion sites. CONCLUSIONS: We propose an AI-driven approach that can assess the robustness of a given ONH solely from a single OCT volume scan of the ONH, and without the need to perform biomechanical testing. Longitudinal studies should establish whether ONH robustness could help us identify fast visual field loss progressors. PRECIS: Using geometric deep learning, we can assess optic nerve head robustness (ie, sensitivity to a change in IOP) from a standard OCT scan that might help to identify fast visual field loss progressors.

Assessment of angle closure disease in the age of artificial intelligence: A review.

Primary angle closure glaucoma is a visually debilitating disease that is under-detected worldwide. Many of the challenges in managing primary angle closure disease (PACD) are related to the lack of convenient and precise tools for clinic-based disease assessment and monitoring. Artificial intelligence (AI)- assisted tools to detect and assess PACD have proliferated in recent years with encouraging results. Machine learning (ML) algorithms that utilize clinical data have been developed to categorize angle closure eyes by disease mechanism. Other ML algorithms that utilize image data have demonstrated good performance in detecting angle closure. Nonetheless, deep learning (DL) algorithms trained directly on image data generally outperformed traditional ML algorithms in detecting PACD, were able to accurately differentiate between angle status (open, narrow, closed), and automated the measurement of quantitative parameters. However, more work is required to expand the capabilities of these AI algorithms and for deployment into real-world practice settings. This includes the need for real-world evaluation, establishing the use case for different algorithms, and evaluating the feasibility of deployment while considering other clinical, economic, social, and policy-related factors.

Rodent genetically modified models of glaucoma.

Glaucoma, one of the leading causes of irreversible blindness worldwide, is a complex and heterogenous disease. While environmental factors are important, it is well-recognized that the disease has a strong heritable component. With the advent of large-cohort genome wide association studies, a myriad of genetic risk loci has been linked to different forms of glaucoma. Animal models have been an indispensable tool in characterizing these loci, especially if they lie within coding regions in the genome. Not only do these models connect genotype to phenotype, advancing our understanding of glaucoma pathogenesis in the process, they also have valuable utility as a platform for the pre-clinical testing of potential therapies. In this review, we will outline genetic models used for studying the major forms of glaucoma, including primary open angle glaucoma, normal tension glaucoma, primary angle closure glaucoma, pigmentary glaucoma, pseudoexfoliation glaucoma, and early onset glaucoma, including congenital and developmental glaucoma, and how studying these models have helped shed light on human glaucoma.

Six-Year Incidence and Risk Factors for Primary Open-Angle Glaucoma and Ocular Hypertension: The Singapore Epidemiology of Eye Diseases Study.

OBJECTIVE: To determine the incidence and risk factors for primary open-angle glaucoma (POAG) and ocular hypertension (OHT) in a multiethnic Asian population. DESIGN: Population-based cohort study. PARTICIPANTS: The Singapore Epidemiology of Eye Diseases study included 10 033 participants in the baseline examination between 2004 and 2011. Of those, 6762 (response rate = 78.8%) participated in the 6-year follow-up visit between 2011 and 2017. METHODS: Standardized examination and investigations were performed, including slit lamp biomicroscopy, intraocular pressure (IOP) measurement, pachymetry, gonioscopy, optic disc examination and static automated perimetry. Glaucoma was defined according to a combination of clinical evaluation, ocular imaging (fundus photo, visual field, and OCT) and criteria given by International Society of Geographical and Epidemiological Ophthalmology. OHT was defined on the basis of elevated IOP over the upper limit of normal; i.e., 20.4 mmHg, 21.5 mmHg, and 22.6 mmHg for the Chinese, Indian, and Malay cohort respectively, without glaucomatous optic disc change. MAIN OUTCOME MEASURES: Incidence of POAG, OHT, and OHT progression. RESULTS: The overall 6-year age-adjusted incidences of POAG and OHT were 1.31% (95% confidence interval [CI], 1.04-1.62) and 0.47% (95% CI, 0.30-0.70). The rate of progression of baseline OHT to POAG at 6 years was 5.32%. Primary open-angle glaucoma incidence was similar (1.37%) in Chinese and Indians and lower (0.80%) in Malays. Malays had higher incidence (0.79%) of OHT than Indians (0.38%) and Chinese (0.37%). Baseline parameters associated with higher risk of POAG were older age (per decade: odds ratio [OR], 1.90; 95% CI, 1.54-2.35; P < 0.001), higher baseline IOP (per mmHg: OR, 1.20; 95% CI, 1.12-1.29; P < 0.001) and longer axial length (per mm: OR, 1.22; 95% CI, 1.07-1.40, P = 0.004). CONCLUSION: Six-year incidence of POAG was 1.31% in a multiethnic Asian population. Older age, higher IOP, and longer axial length were associated with higher risk of POAG. These findings can help in future projections and guide public healthcare policy decisions for screening at-risk individuals. FINANCIAL DISCLOSURE(S): The authors have no proprietary or commercial interest in any materials discussed in this article.