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Introduction: This work aims to determine the effect on nerve fiber layer (NFL) and ganglion cell complex (GCC) thickness trends in eyes with open-angle glaucoma (OAG) treated with Vision Protection Therapy™ (VPT). Methods: A retrospective analysis of spectral-domain optical coherence tomography (OCT) measured NFL and GCC thickness trends was performed, excluding eyes with poor-quality scans and principal diagnoses other than OAG. This study compares eyes with OAG managed conventionally with IOP control alone (controls) to eyes managed with the addition of VPT (VPT eyes). The direction (+ or −) and magnitude (microns/year) of the OCT trends were the study endpoints. Results: Seventy-eight control eyes of 40 patients and 61 VPT-treated eyes of 39 patients were included in the study. Positive NFL trends were noted in 5% of control eyes vs. 71% of VPT eyes (p < 0.0001). Positive GCC trends were noted in 8% of control eyes vs. 43% of VPT eyes (p < 0.0001). Mean NFL trends (µm/year) were − 0.692 for controls vs. 0.347 for VPT (p < 0.0001). Mean GCC trends (µm/year) were − 0.554 for controls vs. − 0.148 for VPT (p = 0.0175). Conclusions: The addition of VPT to the conventional management of OAG resulted in highly significant improvements in NFL and GCC trends, indicating a reversal of key indicators of glaucoma severity and progression. [ABSTRACT FROM AUTHOR]

To assess the impact of genetic risk estimation for primary open-angle glaucoma (POAG) in Japanese individuals. Cross-sectional analysis. Genetic risk scores (GRSs) were constructed based on a genome-wide association study (GWAS) of POAG in Japanese people. A total of 3625 Japanese individuals, including 1191 patients and 2434 controls (Japanese Tohoku), were used for the model selection. We also evaluated the discriminative accuracy of constructed GRSs in a dataset comprising 1034 patients and 1147 controls (the Japan Glaucoma Society Omics Group [JGS-OG] and the Genomic Research Committee of the Japanese Ophthalmological Society [GRC-JOS]) and 1900 participants from a population-based study (Hisayama Study). We evaluated 2 types of GRSs: polygenic risk scores using the pruning and thresholding procedure and a GRS using variants associated with POAG in the GWAS of the International Glaucoma Genetics Consortium (IGGC). We selected the model with the highest areas under the receiver operating characteristic curve (AUC). In the population-based study, we evaluated the correlations between GRS and ocular measurements. Proportion of patients with POAG after stratification according to the GRS. We found that a GRS using 98 variants, which showed genome-wide significance in the IGGC, showed the best discriminative accuracy (AUC, 0.65). In the Japanese Tohoku, the proportion of patients with POAG in the top 10% individuals was significantly higher than that in the lowest 10% (odds ratio [OR], 6.15; 95% confidence interval [CI], 4.35–8.71). In the JGS-OG and GRC-JOS, we confirmed similar impact of POAG GRS (AUC, 0.64; OR [top vs. bottom decile], 5.81; 95% CI, 3.79–9.01). In the population-based study, POAG prevalence was significantly higher in the top 20% individuals of the GRS compared with the bottom 20% (9.2% vs. 5.0%). However, the discriminative accuracy was low (AUC, 0.56). The POAG GRS was correlated positively with intraocular pressure (r = 0.08: P = 4.0 × 10–4) and vertical cup-to-disc ratio (r = 0.11; P = 4.0 × 10–6). The GRS showed moderate discriminative accuracy for POAG in the Japanese population. However, risk stratification in the general population showed relatively weak discriminative performance. Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article. [ABSTRACT FROM AUTHOR]

The etiology of primary open angle glaucoma is constituted by both intraocular pressure-dependent and intraocular pressure-independent mechanisms. However, GWASs of traits affecting primary open angle glaucoma through mechanisms independent of intraocular pressure remains limited. Here, we address this gap by subtracting the genetic effects of a GWAS for intraocular pressure from a GWAS for primary open angle glaucoma to reveal the genetic contribution to primary open angle glaucoma via intraocular pressure-independent mechanisms. Seventeen independent genome-wide significant SNPs were associated with the intraocular pressure-independent component of primary open angle glaucoma. Of these, 7 are located outside known normal tension glaucoma loci, 11 are located outside known intraocular pressure loci, and 2 are novel primary open angle glaucoma loci. The intraocular pressure-independent genetic component of primary open angle glaucoma is associated with glaucoma endophenotypes, while the intraocular pressure-dependent component is associated with blood pressure and vascular permeability. A genetic risk score for the intraocular pressure-independent component of primary open angle glaucoma is associated with 26 different retinal micro-vascular features, which contrasts with the genetic risk score for the intraocular pressure-dependent component. Increased understanding of these intraocular pressure-dependent and intraocular pressure-independent components provides insights into the pathogenesis of glaucoma. The mechanisms connecting intraocular pressure to glaucoma remain unclear. Here, the authors use GWAS by subtraction to reveal intraocular pressure-independent aspects of glaucoma. [ABSTRACT FROM AUTHOR]

Objectives: This study aimed to evaluate the postoperative outcomes of the PreserFlo MicroShunt in Asian patients with exfoliation glaucoma. Methods: We used the Kaplan–Meier method to analyze 29 eyes of 29 patients with exfoliation glaucoma (mean age: 80.7 ± 8.3 years; 16 males; 24 eyes with intraocular lens implants; preoperative intraocular pressure [IOP]: 32.5 ± 9.3 mmHg; preoperative antiglaucoma medications: 3.4 ± 1.0; Asian ethnicity: 100%) who underwent PreserFlo MicroShunt surgery alone at Saneikai Tsukazaki Hospital from November 2022 to November 2023. The criteria for survival were a reduction in IOP of ≥20%, no additional glaucoma surgery, and IOP of 5–21 mmHg (condition 1), 5–18 mmHg (condition 2), and 5–15 mmHg (condition 3). Needling and glaucoma eye drops were considered qualified successes. Results: The mean follow-up period was 27.9 weeks, with a reoperation rate of 31% (9 cases). The complete and qualified success survival rates at 24 weeks were 56%, 52%, and 49%, and 67%, 59%, and 53% for conditions 1–3, respectively. The complete and qualified success survival rates at 48 weeks were 47%, 43%, and 45%, and 52%, 46%, and 48% for conditions 1–3, respectively. Conclusions: The postoperative outcomes of the PreserFlo MicroShunt in Asian patients with exfoliation glaucoma demonstrated an approximate 50% success rate at both 24 and 48 weeks, with a reoperation rate of approximately 30%. Caution is warranted when performing PreserFlo MicroShunt in patients with exfoliation glaucoma. [ABSTRACT FROM AUTHOR]

This study aimed to assess the effectiveness and safety of ab externo canaloplasty over a 3-year follow-up period in Polish Caucasian patients with glaucoma. This retrospective study of a cases series was conducted at the Department of Ophthalmology Medical University of Bialystok, Poland. Primary outcome measures were intraocular pressure and medication burden. Secondary outcome measures were best corrected visual acuity, retinal nerve fiber layer thickness, visual field test results, endothelial cell density, intraoperative and postoperative complications, and additional glaucoma surgery. The study group consisted of 160 eyes diagnosed with early to-moderate primary open-angle glaucoma and treated with ab externo canaloplasty from 2014 to 2020. The criteria for qualified and complete success were intraocular pressure < 18 mmHg or ≥ 20% reduction in intraocular pressure from baseline with or without antiglaucoma medications, respectively. After surgery, the mean intraocular pressure decreased from 19.23 ± 4.33 to 14.52 ± 3.79 mmHg, which constituted a 36.7 ± 7.8% reduction compared to the baseline value. The number of medications decreased by two at the end of the study period (from 2.69 ± 1.05 to 0.32 ± 0.75). Complete and qualified success were achieved in 58.7% and 68.7% of the patients, respectively, at the end of follow-up. An incomplete cannulation of Schlemm's canal was the most common intraoperative complication, occurring in 32 eyes (20%). The most frequent postoperative complications were hyphema, Descemet's membrane detachment, and a transient increase in intraocular pressure. Additional surgical procedure was required in seven cases (4.4%). In 16 patients (10%), medical treatment was re-administered. Overall, our findings suggest that ab externo canaloplasty is a good option for Polish Caucasian patients with primary open-angle glaucoma. It reduces intraocular pressure and has a low postoperative complication rate. Additional glaucoma surgery or re-administration of medications is required if the target intraocular pressure is unsatisfactory. [ABSTRACT FROM AUTHOR]

To assess the level of both pro-inflammatory and anti-inflammatory cytokines in the aqueous humor (AH) of patients suffering from uveitis, with or without coexisting glaucoma, and compare them with patients diagnosed with primary open-angle glaucoma (POAG) and those with age-related cataract (ARC). By using Luminex xMAP® multiplex assays analyses, we assessed levels of 11 cytokines and chemokines, and compared them across groups, including uveitis-secondary glaucoma (USG) (n = 16), uveitis without glaucoma (UwoG), (n = 16), POAG (n = 16), and ARC (n = 16) to explore the correlation between these cytokines and the presence of uveitis, as well as intraocular pressure (IOP). Pro-inflammatory factors MCP-1, MIP-1β, IL-6, IL-8, and transforming growth factors TGF-β1 and TGF-β2 were significantly elevated in the AH of USG eyes. In the case of enhanced anti-inflammatory in the perioperative period, the pro-inflammatory factors remained notably elevated in the USG group compared to the UwoG group (P < 0.01). The levels of IL-6, IL-8, and MCP-1 in the AH of the USG group and POAG group had the same trend, which markedly surpassed those of the ARC group (P < 0.01). Significantly increased levels of MCP-1, MIP-1β, IL-6, IL-8, TGF-β1, and TGF-β2 were found in the AH of USG patients, implying a potential role for these mediators in the progression of glaucomatous manifestations within patients with uveitis. Besides the analysis revealed no discernible statistical disparity in cytokine concentrations within the AH of USG eyes whether the preoperative baseline IOP was greater than 30 mmHg or not, indicating that the safety of antiglaucoma surgery in USG patients even with baseline high IOP. [ABSTRACT FROM AUTHOR]

Purpose: Emerging data suggest that acetaminophen lowers intraocular pressure (IOP) and has the potential to be repurposed as pharmacotherapy to treat open-angle glaucoma. However, pharmacokinetic data are lacking. This study aims to describe the pharmacokinetics of topical acetaminophen and its metabolite [N-arachidonoylaminophenol (AM404)] when administered individually and in combination, and to determine its effect on IOP in the ocular normotensive adult New Zealand White Rabbit (NZWR). Methods: A randomized control trial was conducted using topical 1% acetaminophen and 1% AM404. The study was divided into two sub-studies using both paired-eye and two-eye designs. Results: The mean [95% confidence interval of the mean (95% CI)] concentration of acetaminophen detected in the aqueous humor (AH) was 4.09 ppm (3.18–5.00) at 2 h and 0.92 ppm (0.60–1.24) at 4 h after an immediate dose of topical acetaminophen. The integral IOP, defined as the integral of IOP change from baseline over time, was −5.1 mmHg⋅h (95% CI: −10 to 0.41) for control,−7.5 mmHg⋅h (95% CI: −14 to −1.1) for half-hourly acetaminophen, and −4.4 mmHg⋅h (95% CI: −14 to 5.5) for hourly acetaminophen over a 4-h period. When comparing topical acetaminophen with AM404 dosed half-hourly over a 4-h period, the integral IOP was −2.3 mmHg⋅h (95% CI: −5.9 to 1.3) for control,−2.0 mmHg⋅h (95% CI: −5.6 to 1.7) for AM404, −1.7 mmHg⋅h (95% CI: −4.5 to 1.2) for acetaminophen, and −3.2 mmHg⋅h (95% CI: −5.4 to −0.96) for acetaminophen/AM404 combined. Conclusions: Acetaminophen, but not its metabolite AM404, penetrated the multilayered cornea via passive diffusion in a dose-dependent fashion. There was a nonsignificant tendency to cause a lowering of IOP over the 4-h dosing period with higher AH concentrations of acetaminophen. Topical AM404 did not show a significant IOP-lowering effect. [ABSTRACT FROM AUTHOR]

Background/Objectives: This study aims to evaluate the computed tomography (CT) scans of glaucoma patients using prostaglandin analogs (PGA) in one eye, investigate findings associated with prostaglandin-associated periorbitopathy (PAP), and compare these findings with those of the contralateral eyes. Methods: Patients with open-angle glaucoma who had CT images of the orbital region taken for another reason at least one month after starting PGA treatment in one eye were included in the study. Enophthalmos measurements from thin-slice CT images, along with 3D volume measurements of orbital fat tissue, periorbital muscles, and the optic nerve, were performed. Ophthalmological examination findings and treatment information were collected. The values were compared with those of the contralateral eyes of the same patients not using PGA. Intraclass correlation coefficients (ICCs) were computed to evaluate measurement repeatability. Results: Forty patients were included in the study. Among them, 29 (72.5%) used latanoprost, 9 (22.5%) used bimatoprost, and 2 (5%) used travoprost. The mean enophthalmos values on the treated side (15.5 ± 2.0 mm) were lower than on the untreated side (16.1 ± 1.4 mm), but this difference was not statistically significant (p = 0.07). In 29 patients (72.5%), enophthalmos measurements were smaller on the treated side, with 7 patients (17.5%) showing a difference of 2 mm or more. No significant correlation was found between the duration of PGA use and enophthalmos measurements (p = 0.768 r = −0.048). Additionally, no significant differences were found in orbital fat volume, total extraocular muscle volume, and optic nerve volume (p > 0.05). ICC values demonstrated excellent reliability (ICC > 0.75) for all measurements. Conclusions: We did not find significant differences in enophthalmos measurements, orbital fat volume, total muscle volume, and optic nerve volume between the PGA-treated and untreated eyes. [ABSTRACT FROM AUTHOR]

Purpose: Glaucoma medication may accelerate the progression of presbyopia. The aim of this study was to compare presbyopia between controls and patients with glaucoma in their 40s. Methods: This was a cross-sectional study of bilateral phakic participants aged between 40 and 49, which included controls (n = 114, mean age 46.1 ± 2.7 y) and patients with primary open-angle glaucoma (n = 105, 46.4 ± 2.7 y) who had been using FP receptor agonists, beta blockers, and carbonic anhydrase inhibitors for at least six months. We compared the near add power between the two groups. Results: The mean near add power and the prevalence of symptomatic presbyopia (near add power ≥ 1.50 D) were 1.16 ± 0.74 D and 42.1% for controls and 1.77 ± 0.71 D (p < 0.01) and 79.0% (p < 0.01) for glaucoma patients, respectively. The odds ratio (OR) and confidence interval for symptomatic presbyopia were associated with age (1.36, 1.21–1.52), ganglion cell complex thickness (0.96, 0.94–0.99), presence of glaucoma (6.19, 3.13–12.23), and number of glaucoma medications (4.26, 2.42–7.43). Among medications, only FP receptor agonists (5.79, 2.68–12.32) produced significant results. Survival analysis showed that glaucoma patients reached the threshold of a near add power of +1.50 D significantly sooner than controls (p < 0.05; log-rank test). Conclusions: Glaucoma patients, especially those using FP receptor agonists, had higher near add power than controls. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study is to compare choroidal thickness in juvenile open angle glaucoma (JOAG) and healthy controls using spectral domain optical coherence tomography (SD-OCT) and study its correlations. Methods: In this case–control study, 56 eyes of 28 JOAG patients and an equal number of controls were recruited. SD-OCT was used to measure the choroidal thickness (ChT), in the macular region at 5 locations: subfoveal, 1500 µm and 3000 µm nasal and temporal to the foveal center, and in the peripapillary region at 6 locations: up to 1500 µm, nasal and temporal to the disc, respectively. The ChT and its correlations with age, intraocular pressure, cup-to-disc ratio, central corneal thickness, mean deviation, and axial length were studied. Results: The average macular ChT in JOAG was 306.30 ± 56.49 µm vs. 277.12 ± 64.68 µm in controls. The average peripapillary ChT in JOAG was 197.79 ± 44.05 µm vs. 187.24 ± 38.89 µm in controls. The average total ChT (p = 0.042), the average macular ChT (p = 0.022), the subfoveal ChT (p = 0.022), the ChT 1500 µm (p < 0.001), and 3000 µm temporal to the fovea (p = 0.002) were significantly thicker in the JOAG group. In the JOAG group, the average macular ChT had a significant negative correlation with age, whereas axial length was positively correlated with the average peripapillary ChT. Conclusions: In this South Asian cohort of JOAG, the average total ChT, average macular ChT, subfoveal ChT, and ChT at 1500 µm, and 3000 µm temporal to the fovea were significantly thicker when compared to healthy controls. [ABSTRACT FROM AUTHOR]

Introduction: The purpose of this study is to assess the real-life efficacy and tolerance of a new preservative-free, surfactant-free latanoprost (PFSF-LAT) formulation. Methods: Retrospective, multicentre, non-comparative, observational study in patients with ocular hypertension or open angle glaucoma, naïve or non-naïve to previous intraocular pressure (IOP)-lowering treatment, and treated for at least 3 months with the study eye drop. IOP for worse eye, ocular signs and symptoms, and concomitant use of artificial tears were collected at study drug initiation and at last visit under treatment. Reasons for discontinuing the study eye drop (if relevant) and investigators' satisfaction were also assessed. Results: In the per protocol population (103 eyes; 63 naïve, 39 switched, 1 not classified because of missing data), IOP decreased significantly (p < 0.001) from 21.6 ± 5.0 mmHg at baseline to 16.1 ± 3.5 mmHg at the end of the study (mean reduction of − 5.5 ± 4.6 mmHg; − 25.5%). IOP in naïve patients was significantly improved, with a mean reduction of 7.1 mmHg (− 30.7%), which was within expected latanoprost IOP-lowering effect. Interestingly, in previously treated patients, switching to PFSF-LAT also allowed for a further 2.9 mmHg decrease in IOP (p < 0.001). The incidence of ocular side effects at study initiation was significantly (p < 0.001) reduced from 31.1% to 11.3% in the overall population, and from 65.0% to 7.5% in switched patients. This included conjunctival hyperaemia and superficial punctate keratitis (from 42.5% to 2.5% and from 37.5% to 2.5% in switched patients, respectively). According to investigators, tolerance and efficacy of the study eye drop were satisfactory or very satisfactory in 98.1% and 83.2% of patients, respectively. Conclusion: PFSF-LAT is an efficient treatment for patients with glaucoma with an improved tolerance profile. It can be considered as initial therapy in naïve patients or in patients with poor ocular tolerance to previous IOP-lowering eye drops. [ABSTRACT FROM AUTHOR]

Objective: The relationship between smoking and onset of glaucoma has been inconsistent. However, there is a gap in understanding whether tobacco smoking is linked to a worse visual impairment in different glaucoma subtypes. The objective of this study was to examine the association between smoking behavior and vision-related disability in people who have different glaucoma subtypes. Methods: A total of 283 people with primary open-angle glaucoma (POAG), primary angle closure glaucoma (PACG), normal tension glaucoma (NTG), and pseudo-exfoliative (PEX) were included in this cross-sectional study. The recruitment of study participants was organized in one of two tertiary centers for eye diseases in Belgrade, Serbia, during their regular eye checks. Information about the duration and quantity of smoking was self-reported. Vision-related impairment was quantified using a validated Glaucoma Quality of Life-15 (GQL-15) questionnaire. Results: A series of multiple linear regression models adjusted for age, gender, severity of glaucoma, lifestyle, and mobility, intraocular pressure level, visual parameters, previous and current therapy, and chronic illnesses suggested that a higher quantity of cigarettes smoked per day was associated with poorer vision-related quality of life only among people with NTG subtypes. This association was absent when smoking duration was tested in the adjusted linear regression model. Conclusion: A higher number of cigarettes smoked daily was associated with poorer vision-related impairment among people who have NTG, but not other glaucoma subtypes. It is recommended that ophthalmologists and other health-care professionals work to improve their patients' understanding of harmful effects of tobacco smoke and quit smoking. [ABSTRACT FROM AUTHOR]

Background/Objectives: Recent prospective studies have shown that selective laser tra-beculoplasty (SLT) is a safe and cost-effective alternative to pressure-reducing eye drop therapy as a first-line treatment for ocular hypertension or open-angle glaucoma. In addition to its comparable efficacy to eye drop therapy, SLT has been particularly effective in delaying the time until a surgical intervention is needed. The aim of our evaluation is to analyze patients who have received SLT following a pressure-reducing procedure. The primary endpoint is the duration until a subsequent interventional or surgical procedure is required. Methods: A retrospective analysis of 98 patients who underwent selective laser trabeculoplasty following a previous pressure-reducing procedure between 2017 and 2023. The statistical analyses included Cox regression and Kaplan–Meier survival estimations. Results: In total, 122 eyes of 98 patients received selective laser trabeculoplasty following a previous pressure-reducing procedure at the Department of Ophthalmology in Freiburg. The median follow-up period was 381.5 days (range 43.25–862.75 days). Approximately 68% of the eyes did not require another pressure-reducing procedure 365 days after the intervention, while about 58% of the eyes remained without another procedure after 730 days, according to Kaplan–Meier analysis. No significant difference was found between the different types of glaucoma regarding the duration until a subsequent pressure-reducing procedure was needed. The study indicated a tendency for patients with pseudoexfoliation glaucoma to undergo a secondary intervention earlier compared to those with primary open-angle glaucoma (p = 0.16). The intraocular pressure before SLT had a significant impact on the duration until the subsequent operation (p = 0.005). Conclusions: SLT is an effective method even after a previous pressure-reducing procedure for patients in whom further pressure-reducing interventions need to be delayed. [ABSTRACT FROM AUTHOR]

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Purpose: To compare the macular and optic disc vascular parameters in the unaffected fellow eyes of subjects with unilateral pseudoexfoliation syndrome (PXS) and controls using optical coherence tomography angiography (OCTA). Methods: The medical records of 61 eyes of 61 patients were analyzed in a retrospective study. Of these, 30 eyes were unaffected fellow eyes and 31 eyes were control eyes. The vessel density (VD), perfusion density (PD) and foveal avascular zone (FAZ)-related parameters of the superficial capillary plexus (SCP) in the circumpapillary and macular area and the VD and PD of the deep capillary plexus (DCP) in the macular area were measured using OCTA after dilatation and were compared between two groups after adjustment for age, sex and axial length. Results: There were no statistically significant differences in sex ratio or mean age, central corneal thickness measurements, refractive errors, intraocular pressures and axial length between both groups (all P > 0.05). In the circumpapillary area, inferior VD and PD in the inner zone, as well as average, temporal, inferior, and nasal VD and PD in the outer zone were significantly reduced in the unaffected fellow eyes with unilateral PXS, while the circumpapillary retinal nerve fiber layer (RNFL) thicknesses were similar between groups. In the macular SCP, VDs were significantly lower in all sectors in the inner area and in the outer zones (p < 0.05 for all), PDs were significantly lower in all sectors (p < 0.05 for all) except the nasal sector of the outer zone (p = 0.003 for average, p = 0.029 for superior sector, p = 0.004 for temporal sector, p < 0.001 for inferior sector), and the FAZ circularity (p = 0.037) were significantly lower in the unaffected fellow eyes with unilateral PXS, whereas macular ganglion cell inner plexiform layer (GCIPL) thickness was similar between the two groups. Conclusions: Although circumpapillary RNFL and GCIPL thicknesses were similar between the two groups, VDs and PDs in the circumpapillary and macular SCP and FAZ circularity were significantly lower in the fellow eye of subjects with unilateral PXS. [ABSTRACT FROM AUTHOR]

The complexity of branching and curvilinear morphology of a complete mitochondrial network within each cell is challenging to analyze and quantify. To address this challenge, we developed an image analysis technique using persistent homology with a multiparameter filtration framework, combining image processing techniques in mathematical morphology. We show that such filtrations contain both topological and geometric information about complex cellular organelle structures, which allows a software program to extract meaningful features. Using this information, we also develop a connectivity index that describes the morphology of the branching patterns. As proof of concept, we utilize this approach to study how mitochondrial networks are altered by genetic changes in the Optineurin gene. Mutations in the autophagy gene Optineurin (OPTN) are associated with primary open-angle glaucoma (POAG), amyotrophic lateral sclerosis (ALS), and Paget's disease of the bone, but the pathophysiological mechanism is unclear. We utilized the proposed mathematical morphology-based multiparameter filtration and persistent homology approach to analyze and quantitatively compare how changes in the OPTN gene alter mitochondrial structures from their normal interconnected, tubular morphology into scattered, fragmented pieces. [ABSTRACT FROM AUTHOR]

Purpose: To investigate whether it is better to perform minimally invasive glaucoma surgery (MIGS) when performing cataract surgery on glaucoma patients. Methods: The study enrolled a total of 159 eyes of subjects with mild-to-moderate glaucoma, including primary open angle glaucoma (POAG), normal tension glaucoma (NTG), and combined mechanism glaucoma (CMG) with visually significant cataract, who were treated with one or more ophthalmic antiglaucoma agents. Phacoemulsification and aspiration with intraocular lens insertion (PEA + IOL, phaco group) or MIGS with PEA + IOL (µLot-phaco group) was performed on patients with glaucoma. Age, sex, glaucoma type, pre- and postoperative IOP, and ratio of IOP reduction were estimated. Results: The rate of IOP reduction in the µLot-phaco group was found to be significantly higher than in the phaco group at the 6-month postoperative assessment. Specifically, a strong correlation was observed between preoperative IOP levels, the presence of POAG, and patient age within the µLot-phaco group, all of which contributed significantly to the IOP reduction observed at the 6-month follow-up. Conclusions: Simultaneous cataract and MIGS were found to be more effective in older POAG patients with higher preoperative IOP. [ABSTRACT FROM AUTHOR]

PurposeMethodsResultsConclusionsTo investigate racial and ethnic inequalities in prescription of Netarsudil, one of two anti-glaucoma medications with a novel mechanism to be introduced in the past two decades, among patients with primary open-angle glaucoma.This retrospective cohort matched study, based on electronic health records consisting of 92 million patients in the U.S, utilized Propensity Score Match, Relative Risk, Kaplan–Meier survival, and Chi-Square analysis to identify differences in rates of Netarsudil prescribing between racial and ethnic groups (non-Hispanic White, non-Hispanic Black, non-Hispanic Other Race, and Hispanic).Among the sample of patients that met Primary Open-Angle Glaucoma inclusion criteria (55,942), more White patients were prescribed Netarsudil than Black; (RR:1.24, 95% CI: 1.15-1.34) and Hispanic; (RR:1.63, 95% CI: 1.29-2.07) patients. White patients had higher prescription rates than Black patients in the Midwest (6.5% vs 4.2%; p < 0.0001) and West (11.2% vs 7.1%; p = 0.0002), higher rates than Hispanic patients in the South (4.9% vs. 2.0%; p < 0.0001) and West (11.2% vs. 7.8%; p < 0.008), but lower rates than Black patients in the Northeast (7.2% vs. 13.2%; p < 0.0001).Differences in Netarsudil prescription rates within the United States exist between White and Black patients, and White and Hispanic patients. These differences exist when stratified by regions within the U.S. by varying degrees. Future studies are needed to investigate factors contributing to disparities in accessing new medications and to identify ways to eliminate such barriers to improve equity in care of glaucoma patients, especially among those historically disadvantaged. [ABSTRACT FROM AUTHOR]

This study investigated gaze behavior during visuo-cognitive-motor tasks with a change of movement direction in glaucoma patients and healthy controls. Nineteen glaucoma patients (10 females, 9 males) and 30 healthy sighted controls (17 females, 13 males) participated in this cross-sectional study. Participants performed two visuo-cognitive-motor tasks with a change of movement direction: (i) the "Speed-Court-Test" that involved stepping on different sensors in response to a visual sign displayed on either a large or small screen (165″ and 55″, respectively); (ii) the "Trail-Walking-Test" that required walking to 15 cones labeled with numbers (1–8) or letters (A-G) in an alternately ascending order. During these tasks, the time needed for completing each task was determined and the gaze behavior (e.g., saccade duration, fixation duration) was recorded via eye tracking. Data were analyzed with repeated measures analyses of covariance (ANCOVA; GROUP × SCREEN) and one-way ANCOVA. No differences between groups were found for the time needed to complete the tasks. However, during the "Trail-Walking-Test", the fixation duration was longer for glaucoma patients than for controls (p = 0.016, η p 2 = 0.131). Furthermore, during the "Speed-Court-Test", there was a screen size effect. Irrespective of group, saccade amplitudes were lower (p < 0.001, η p 2 = 0.242) and fixation durations were higher (p = 0.021, η p 2 = 0.125) for the small screen. Fixation durations were longer in glaucoma patients during the cognitively demanding "Trail-Walking-Test", which might indicate a strategy to compensate for their visual impairment. [ABSTRACT FROM AUTHOR]

Background Methods Results Conclusions Effective clinical implementation of polygenic risk testing for glaucoma relies on healthcare professionals' attitudes and knowledge of the test. Given the emerging applications of the test, it will likely impact a range of healthcare professionals and will require competency in polygenic risk scores concepts for all those involved in patient care. To our knowledge, this is the first study to assess healthcare professionals' views towards polygenic testing for glaucoma.An online cross‐sectional questionnaire was distributed to healthcare professionals via relevant professional organisations in Australia. The questionnaire assessed experience and confidence with genetic testing, glaucoma and genetic knowledge, recommendations for the tests, and factors affecting the decision.A total of 94 participants completed the questionnaire. The sample was composed of ophthalmologists (36%), optometrists (21%), orthoptists (17%), general practitioners (16%) and clinical geneticists/genetic counsellors (10%). Although familiarity with polygenic risk scores for glaucoma was low overall (11%), the majority reported a positive attitude towards recommending testing based on known risk factors such as family history (91%) and older age (57%). Over 95% indicated that ophthalmologists would be the most appropriate group to order polygenic risk testing and communicate results. The majority felt they would benefit from more training on polygenic risk scores (93%).Our findings indicated that multiple groups of healthcare professionals were neither familiar nor confident with the concept of glaucoma polygenic risk testing, and identified training and education needs to support the implementation of testing into clinical practice. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to determine the prevalence of anxiety and depression among patients with glaucoma compared to the average Brazilian prevalence (9.8% of anxiety and 5.8% of depression, according to the World Health Organization) and its correlation with the severity of the disease. Methods: This was a transversal, single-arm trial of patients from four glaucoma centers in São Paulo and Curitiba--Brazil. Patients comprised adults at least 18 years of age with glaucoma diagnosis under treatment for at least 6 months. All subjects of the study answered two questionnaires (PHQ-9 and GAD-7) to evaluate the presence of anxiety and depression, and the results were analyzed accordingly to clinical and demographic characteristics. Results: The protocol included a total of 210 patients. The average age was 61.6 ± 15.3 years, and the female gender was more common (68.86%). Primary open-angle glaucoma was the most common diagnosis (59.90%). The average IOP was 18.5 mmHg, and 1.5 anti-glaucoma drops were the mean treatment. The prevalence of depression and anxiety was 26.90 and 25.71%, respectively. Most patients with anxiety were classified as early glaucoma, while those with depression had severe glaucoma. Conclusion: This study found that the prevalence of anxiety and depression among patients with glaucoma is higher than in the general population in our country. [ABSTRACT FROM AUTHOR]

Purpose Methods Results Conclusion Prospective investigation to determine the prevalence of ocular melanosis in adult Cairn Terriers within the United Kingdom using a previously established staging scheme.Ophthalmic assessment was performed on adult Cairn Terriers, recruited from various geographic locations within the United Kingdom. Examination included gonioscopy, rebound tonometry, slit lamp biomicroscopy, and indirect ophthalmoscopy, performed by one examiner (AM).A total of 93 dogs were examined, including 52 females and 41 males, aged between 15 months and 16 years 4 months. Sixty of 93 dogs (64.5%) were >7 years of age. Nine of 93 dogs (9.6%) demonstrated changes consistent with ocular melanosis. Four of 9 (44.4%) had Stage 1 disease and 5 of 9 (55.6%), Stage 2. Stages 3 or 4 were not identified in any dogs. Mean intraocular pressures in affected and unaffected dogs were 14.7 mmHg (range 12–17 mmHg) and 12.8 mmHg (range 5–21 mmHg), respectively. Incomplete pupil dilation was noted in affected dogs following pharmacologic mydriasis.Ocular melanosis was identified in approximately 10% of examined dogs, over half were dogs of breeding age (<7 years of age). It is possible that Grade 1 disease could go undetected, prior to obvious scleral pigment accumulation (Grade 2 disease). It is therefore recommended that dogs undergoing pre‐breeding screens have pre‐dilation assessment of the anterior segment using slit lamp biomicroscopy with subsequent gonioscopy to clearly assess for circumferential thickening of the iris base that might otherwise go undetected. Additionally, regular reassessment of breeding dogs is advised as disease progression could be rapid. [ABSTRACT FROM AUTHOR]

Glaucoma is a widespread ophthalmological disease, with a high impact and frequent visual morbidity. While the physiopathology of the two types of primary glaucoma (open angle and angle closure) has been studied, there seems to be little relationship between the two. In this study, we gather clinical and preclinical data to support the idea that the two primary glaucomas are "mirrored" in terms of morphological parameters and disease physiopathology. In short, primary angle closure glaucoma (PACG) is associated with hyperopia and low axial length, and primary open angle glaucoma (POAG) is associated with myopia and high axial length. Moreover, in PACG and in primary angle closure or primary angle closure suspect cases, while there is extensive iridotrabecular contact, the intraocular pressure (IOP) is still maintained in the lower half of the normal range throughout the evolution of the disease, which suggests a baseline trabecular hyperfiltration in PACG. In the opposite case, myopic eyes with open angles and a higher risk of developing POAG often have a baseline IOP in the upper half of the normal range, suggesting a baseline trabecular hypofiltration. As we explore clinical, genetic and animal model data regarding these opposing aspects, we hypothesize the existence of a mirroring relationship between PACG and POAG. Defining the relationship between the two potentially blinding diseases, with a high prevalence worldwide, may aid in understanding the mechanisms better and refining diagnosis and treatment. Thus, our theory has been named the Mirror Theory of Primary Glaucomas. [ABSTRACT FROM AUTHOR]

Purpose: Investigate the oxylipin profiles in the aqueous humor of primary open-angle glaucoma (POAG) patients. Methods: Aqueous humor samples were collected from 17 POAG patients and 15 cataract subjects and subjected to a liquid chromatography/mass spectrometry (LC-MS) analysis to detect the oxylipins. The prediction potential of the differential abundant oxylipins was assessed by the receiver operating characteristic (ROC) curves. Pathway and correlation analyses on the oxylipins and clinical and biochemical parameters were also conducted. Results: The LC-MS analysis detected a total of 76 oxylipins, of which 29 oxylipins reached the detection limit. The multivariate analysis identified five differential abundant oxylipins, 15-keto-prostaglandin F2 alpha (15-kPGF2α), Leukotriene B4 (LTB4), 12,13-Epoxyoctadecenoic acid (12,13-Epome), 15-Hydroxyeicosatetraenoic acid (15-HETE) and 11-Hydroxyeicosatetraenoic acid (11-HETE). The five oxylipins are enriched in the arachidonic acid metabolism and linoleic acid metabolism pathways. Pearson correlation analysis showed that 11-HETE was positively correlated with intraocular pressure and central corneal thickness and negatively with cup/disk area ratio in the POAG patients. In addition, 15-kPGF2α was moderately and positively correlated with the mean deviation (MD) of visual field defect, and LTB4 was moderately and negatively correlated with macular thickness. Conclusions: This study revealed the oxylipin profile in the aqueous humor of POAG patients. Oxylipins involved in the arachidonic acid metabolism pathway could play a role in POAG, and anti-inflammatory therapies could be potential treatment strategies for POAG. [ABSTRACT FROM AUTHOR]

In spite of available treatment options, glaucoma continues to be a leading cause of irreversible blindness in the world. Current glaucoma medications have multiple limitations including: lack of sustained action; requirement for multiple dosing per day, ocular irritation and limited options for drugs with different mechanisms of action. Previously, we demonstrated that pregabalin, a drug with high affinity and selectivity for CACNA2D1, lowered IOP in a dose-dependent manner. The current study was designed to evaluate pregabalin microemulsion eye drops and to estimate its efficacy in humans using in silico methods. Molecular docking studies of pregabalin against CACNA2D1 of mouse, rabbit, and human were performed. Pregabalin microemulsion eye drops were characterized using multiple in vivo studies and its stability was evaluated over one year at different storage conditions. Molecular docking analyses and QSPR of pregabalin confirmed its suitability as a new IOP-lowering medication that functions using a new mechanism of action by binding to CACNA2D1 in all species evaluated. Because of its prolonged corneal residence time and corneal penetration enhancement, a single topical application of pregabalin ME can provide an extended IOP reduction of more than day in different animal models. Repeated daily dosing for 2 months confirms the lack of any tachyphylactic effect, which is a common drawback among marketed IOP-lowering medications. In addition, pregabalin microemulsion demonstrated good physical stability for one year, and chemical stability for 3–6 months if stored below 25 °C. Collectively, these outcomes greatly support the use of pregabalin eye drops as once daily IOP-lowering therapy for glaucoma management. [Display omitted] • Molecular docking analyses estimate strong binding affinity of pregabalin, a novel therapy for open angle glaucoma • Pregabalin microemulsion eye drops supports once daily use by extending the precorneal drug residence time up to 24 h • Pregabalin microemulsion eye drops didn't have any tachyphylactic effect upon repeated dosing for 2 months • Pregabalin microemulsion eye drops is chemically stable for 3–6 month at temperature below 25 °C. [ABSTRACT FROM AUTHOR]

Purpose: The success of XEN Gel Stent (XEN) and Preserflo MicroShunt (Preserflo) implantation depends mainly on the development of bleb fibrosis. This study aimed to describe the histological findings of bleb fibrosis after XEN and Preserflo surgery. Methods: This retrospective study included patients with different types of glaucoma who underwent revision surgery after XEN or Preserflo implantation. The available clinical information and histological samples of removed fibrotic tissue were analyzed. Results: Thirty-six patients were included. Revision surgery was performed at a median of 195 (range = 31–1264) days after primary surgery. The mean intraocular pressure changed from 29.1 (± 10.3) mmHg at baseline to 18.3 (± 8.7) mmHg (− 37%; p < 0.0001) and 16.2 (± 4.2) mmHg (− 45%; p < 0.0001) after 6 and 12 months, respectively. Histological analysis revealed an increase in activated fibroblasts and macrophages in all specimens and a parallel orientation of fibroblasts in a minor part of the probe in 60% of the specimens. No pronounced inflammatory reaction in the form of lymphocytic or granulocytic infiltration was observed. The comparison of specimens from uveitic glaucoma and primary open-angle glaucoma patients revealed no significant differences. Conclusions: The histological analysis of fibrotic blebs from the XEN and Preserflo implants did not show any pronounced immune or foreign-body reaction and revealed a similar histological pattern of failed blebs after trabeculectomy. [ABSTRACT FROM AUTHOR]

Treatment of primary open-angle glaucoma has centered on the lowering of intraocular pressure that damages the optic nerve; however, this strategy is not uniformly successful, especially in normal tension glaucoma, and there is interest in antioxidant, anti-inflammatory, and other neuroprotective strategies. Vegetarian diets are known to be rich in antioxidant and anti-inflammatory components and have a number of established health benefits. Thus, it would be reasonable to assume that vegetarian diets would be beneficial in glaucoma, but this approach has not been well studied. We examine the possible role of vegetarian diets and their components in the incidence and progression of glaucoma. [ABSTRACT FROM AUTHOR]

To examine if 12.5 μl timolol maleate 0.5% microdrops dispensed with the Nanodropper Adaptor provide noninferior intraocular pressure (IOP) reduction compared with conventional 28 μl drops in patients with open-angle glaucoma (OAG) and ocular hypertension (OHT). Prospective, noninferiority, parallel, multicenter, single-masked, active-controlled, randomized trial. Treatment-naïve subjects who were recently diagnosed with OAG and OHT at the Aravind Eye Care System. Both eyes of subjects received 1 commercially available drop or both eyes of subjects received 1 microdrop of timolol maleate 0.5%. We measured IOP, resting heart rate (HR), and blood pressure (BP) at baseline and 1, 2, 5, and 8 hours after timolol administration. The IOP was the primary outcome measure. Secondary outcomes were resting HR, systolic BP (sBP), and diastolic BP (dBP). Adaptor-mediated microdrops and conventional drops of timolol significantly decreased IOP compared with baseline at all timepoints. Noninferiority was established at 3 of 4 timepoints. Heart rate decreases with Nanodropper were approximately 3 beats per minute (bpm) less than with conventional drops. Timolol microdrops appear to be as effective in ocular hypotensive action as conventional drops with a slightly attenuated effect on resting HR and BP. Proprietary or commercial disclosure may be found after the references. [ABSTRACT FROM AUTHOR]

To evaluate the safety and intraocular pressure (IOP)-lowering efficacy of 2 models of the travoprost intraocular implant (fast-eluting [FE] and slow-eluting [SE] types) from 1 of 2 phase 3 trials (the GC-010 trial). Multicenter, randomized, double-masked, sham-controlled, noninferiority trial. Patients with open-angle glaucoma or ocular hypertension having an unmedicated baseline mean diurnal IOP (average of 8 am , 10 am , and 4 pm time points) of ≥ 21 mmHg, and IOP of ≤ 36 mmHg at each of the 8 am , 10 am , and 4 pm timepoints at baseline. Study eyes were randomized to the travoprost intraocular implant (FE implant [n = 200] or SE implant [n = 197] model) or to timolol ophthalmic solution 0.5% twice daily (n = 193). The primary outcome was mean change from baseline IOP in the study eye at 8 am and 10 am , at each of day 10, week 6, and month 3. Safety outcomes included adverse events (AEs) and ophthalmic assessments. Mean IOP reduction from baseline over the 6 time points ranged from 6.6 to 8.4 mmHg for the FE implant group, from 6.6 to 8.5 mmHg for the SE implant group, and from 6.5 to 7.7 mmHg for the timolol group. The primary efficacy end point was met; the upper limit of the 95% confidence interval of the difference between the implant groups and the timolol group was < 1 mmHg at all 6 time points. Study eye AEs, most of mild or moderate severity, were reported in 21.5%, 27.2%, and 10.8% of patients in the FE implant, SE implant, and timolol groups, respectively. The most common AEs included iritis (FE implant, 0.5%; SE implant, 5.1%), ocular hyperemia (FE implant, 3.0%; SE implant, 2.6%), reduced visual acuity (FE implant, 1.0%; SE implant, 4.1%; timolol, 0.5%), and IOP increased (FE implant, 3.5%; SE implant, 2.6%; timolol, 2.1%). One serious study eye AE occurred (endophthalmitis). The travoprost intraocular implant demonstrated robust IOP reduction over the 3-month primary efficacy evaluation period after a single administration. The IOP-lowering efficacy in both implant groups was statistically and clinically noninferior to that in the timolol group, with a favorable safety profile. Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article. [ABSTRACT FROM AUTHOR]

Introduction: This study was conducted to analyze and compare the intraocular pressure (IOP) treatment effect of the slow-eluting (SE) travoprost intracameral implant to the IOP treatment effect of topical prostaglandin analog (PGA) monotherapy in a subgroup of subjects who were on pre-study PGA monotherapy prior to enrollment in the two pivotal phase 3 trials of the travoprost intracameral implant. Methods: A combined study population of 133 subjects from two phase 3 trials, who were on topical PGA monotherapy at screening, subsequently underwent a washout period from their topical PGA, and then were randomized and administered an SE travoprost intracameral implant. The subjects were analyzed for the IOP treatment effects of the pre-study topical PGA monotherapy and the in-study SE travoprost intracameral implant. Paired t-tests were used to compare the difference in screening minus post-washout baseline IOP versus month 3 minus post-washout baseline IOP. The IOP-lowering efficacy in eyes administered an SE travoprost intracameral implant was compared to the IOP lowering in the same eyes while on a topical PGA monotherapy prior to study entry. Results: Pre-study topical PGA monotherapy and the SE travoprost intracameral implant demonstrated IOP treatment effects of −5.76 mmHg and −7.07 mmHg, respectively. The IOP-lowering treatment effect was significantly greater by 1.31 mmHg for the SE travoprost intracameral implant relative to pre-study PGA monotherapy (95% confidence interval: −2.01, −0.60; P = 0.0003). Conclusions: The SE travoprost intracameral implant demonstrated superior IOP-lowering treatment effect versus pre-study topical PGA monotherapy with a superiority margin that was both statistically significant and clinically meaningful. The greater IOP reduction from baseline while on the SE implant versus pre-study topical PGA monotherapy may be a reflection of the optimized adherence and continuous elution of PGA therapy into the anterior chamber achieved with the SE travoprost intracameral implant. Trial Registration: ClinicalTrials.gov identifiers, NCT03519386 and NCT03868124. [ABSTRACT FROM AUTHOR]

Glaucoma is the second leading cause of blindness worldwide and is, in most cases, a consequence of elevated intraocular pressure (IOP), ultimately resulting in the death of retinal ganglion cells (RGCs). Current treatments are mostly focused on normalizing IOP, but we propose the additional use of neuroprotective agents, including methylene blue (MB), to block the loss of RGCs. Wistar rats were subjected to episcleral vein cauterization (EVC) in the left eye while the right eye was sham-operated. One week later, they were divided into two groups, which were injected with either 2.0 mg/kg MB or phosphate-buffered saline (PBS), twice a day, for 7 days. Fifteen days after surgery, rats were tested with scotopic electroretinography (ERG) or pattern electroretinography (PERG). After sacrifice, the number of RGCs and the thickness of the inner retina (IR) were evaluated both in the peripheral and central areas of the retina. Scotopic ERG showed a marked reduction (p < 0.0001) on the a- and b-wave amplitude and oscillatory potential (OP) complexity of the eyes subjected to EVC. These parameters were significantly (p < 0.01) restored by the application of MB. PERG indicated that EVC was responsible for a very significant decrease in N2 amplitude (p < 0.0001) and prolongation of N2 implicit time (p < 0.0001). Treatment with MB significantly restored N2 amplitude (p < 0.0001). In parallel with the ERG results, morphological analysis showed a significant loss of RGCs (p < 0.0001) and IR thickness (p < 0.0001) in both the peripheral and central retinas subjected to EVC, which was significantly prevented (p < 0.0001) by MB treatment. We have shown that MB treatment can be effective in preventing physiological and morphological hallmarks of optic neuropathy in a model of ocular hypertension, which faithfully recapitulates human open-angle glaucoma. Due to its high safety profile, this drug could therefore represent a new pharmacologic strategy to prevent vision loss in glaucoma patients. [ABSTRACT FROM AUTHOR]

Background and Objectives: This study investigates the relationship between thyroid eye disease (TED) and open-angle glaucoma (OAG), focusing on disease severity and clinical features. Materials and Methods: Conducted at the Timis County Emergency Clinical Hospital, the research included 106 patients, with 53 having both conditions and 53 having only OAG. Key metrics analyzed included intraocular pressure (IOP) using a Goldmann applanation tonometer, the retinal nerve fiber layer (RNFL) thickness, and optic nerve head (ONH) characteristics evaluated using optical coherence tomography (OCT). Results: Results indicated that patients with both TED and OAG experienced a 6.09% reduction in RNFL thickness and showed more rapid disease progression, with 48.35% having active TED. The mean IOP in TED patients was 27.5 ± 4.9 mmHg, which was similar to those with only OAG. Demographic factors, including age and gender, influenced the clinical course and disease severity. Conclusions: These findings underscore the importance of specialized monitoring and treatment strategies for patients with coexisting TED and OAG to prevent vision loss. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to compare the safety and effectiveness of intraocular pressure reduction between micropulse transscleral cyclophotocoagulation and “slow cook” transscleral cyclophotocoagulation in patients with refractory primary open-angle glaucoma. Methods: We included patients with primary open angle glaucoma with at least 12 months of follow-up. We collected and analyzed data on the preoperative characteristics and postoperative outcomes. The primary outcomes were a reduction of ≥20% of the baseline value (criterion A) and/or intraocular pressure between 6 and 21 mmHg (criterion B). Results: We included 128 eyes with primary open-angle glaucoma. The preoperative mean intraocular pressure was 25.53 ± 6.40 and 35.02 ± 12.57 mmHg in the micropulse- and “slow cook” transscleral cyclophotocoagulation groups, respectively (p<0.001). The mean intraocular pressure was reduced significantly to 14.33 ± 3.40 and 15.37 ± 5.85 mmHg in the micropulse- and “slow cook” transscleral cyclophotocoagulation groups at the last follow-up, respectively (p=0.110). The mean intraocular pressure reduction at 12 months was 11.20 ± 11.46 and 19.65 ± 13.22 mmHg in the micropulse- and “slow cook” transscleral cyclophotocoagulation groups, respectively (p<0.001). The median preoperative logMAR visual acuity was 0.52 ± 0.69 and 1.75 ± 1.04 in the micropulse- and “slow cook” transscleral cyclophotocoagulation groups, respectively (p<0.001). The mean visual acuity variation was -0.10 ± 0.35 and -0.074 ± 0.16 in the micropulse- and “slow cook” transscleral cyclophotocoagulation, respectively (p=0.510). Preoperatively, the mean eye drops were 3.44 ± 1.38 and 2.89 ± 0.68 drugs in the micropulse- and “slow cook” transscleral cyclophotocoagulation groups, respectively (p=0.017), but those were 2.06 ± 1.42 and 1.02 ± 1.46 at the end of the study in the slow cook” and micropulse transscleral cyclophotocoagulation groups, respectively (p<0.001). The success of criterion A was not significant between both groups. Compared with 11 eyes (17.74%) in the slow cook” transscleral cyclophotocoagulation group, 19 eyes (28.78%) in the micropulse transscleral cyclophotocoagulation group showed complete success (p=0.171). For criterion B, 28 (42.42%) and 2 eyes (3.22%) showed complete success after micropulse- and slow cook” transscleral cyclophotocoagulation, respectively (p<0.001). Conclusion: Both techniques reduced intraocular pressure effectively. [ABSTRACT FROM AUTHOR]

Summary: Glaucoma is a major cause of blindness and vision impairment worldwide, and visual field (VF) tests are essential for monitoring the conversion of glaucoma. While previous studies have primarily focused on using VF data at a single time point for glaucoma prediction, there has been limited exploration of longitudinal trajectories. Additionally, many deep learning techniques treat the time‐to‐glaucoma prediction as a binary classification problem (glaucoma Yes/No), resulting in the misclassification of some censored subjects into the nonglaucoma category and decreased power. To tackle these challenges, we propose and implement several deep‐learning approaches that naturally incorporate temporal and spatial information from longitudinal VF data to predict time‐to‐glaucoma. When evaluated on the Ocular Hypertension Treatment Study (OHTS) dataset, our proposed convolutional neural network (CNN)‐long short‐term memory (LSTM) emerged as the top‐performing model among all those examined. The implementation code can be found online (https://github.com/rivenzhou/VF_prediction). [ABSTRACT FROM AUTHOR]

Background: High myopia is one of the major causes of visual impairment and has an ever-increasing prevalence, especially in East Asia. It is characterized by excessive axial elongation, leading to various blinding complications that extend beyond mere refractive errors and persist immovably after refractive surgery, presenting substantial public health challenge. Main text: High myopia-related complications include lens pathologies, atrophic and tractional maculopathy, choroidal neovascularization, peripheral retinal degenerations and retinal detachment, and glaucoma and heightened susceptibility to intraocular pressure (IOP) elevation. Pathological lens changes characteristic of high myopia include early cataractogenesis, overgrowth of lens, weakened zonules, and postoperative capsular contraction syndrome, possibly driven by inflammatory pathogenesis, etc. Dome-shaped macula and cilioretinal arteries are two newly identified protective factors for central vision of highly myopic patients. These patients also face risks of open-angle glaucoma and IOP spike following intraocular surgery. Morphologic alternations of optic nerve in high myopia can complicate early glaucoma detection, necessitating comprehensive examinations and close follow-up. Anatomically, thinner trabecular meshwork increases this risk; conversely lamina cribrosa defects may offer a fluid outlet, potentially mitigating the pressure. Notably, anxiety has emerged as the first recognized extra-ocular complication in high myopia, with an underlying inflammatory pathogenesis that connects visual stimulus, blood and brain. Conclusions: High myopia induces multiple ocular and potential mental health complications, underscoring the need to develop more effective strategies to improve both physical and emotional well-being of these patients, among which anti-inflammation might possibly represent a promising new target.

Glaucoma, a blinding eye disease with optic neuropathy, is usually associated with elevated intraocular pressure (IOP). The currently available pharmacological and surgical treatments for glaucoma have significant limitations and side effects, which include systemic reactions to medications, patient non-compliance, eye infections, surgical device failure, and damage to the eye. Here, we present Sensor-Actuator-Modulator (SAM), an engineered double mutant version of the bacterial stretch-activated mechanosensitive channel of large conductance (MscL) that directly senses tension in the membrane lipid bilayer of cells and in response, transiently opens its large nonspecific pore to release cytoplasmic fluid. The heterologously expressed mechanosensitive SAM channel acts as a tension-activated pressure release valve in trabeculocytes. In the trabecular meshwork (TM), SAM is activated by membrane stretch caused by elevated IOP. We have identified several SAM variants that are activated at physiologically relevant pressures. Using this barogenetic technology, we have demonstrated that SAM is functional in cultured TM cells, and successfully transduced in vivo in TM cells by use of AAV2/8. Further, it is effective in enhancing aqueous humor outflow facility leading to lowering the IOP in a mouse model of ocular hypertension. [ABSTRACT FROM AUTHOR]

Purpose: To assess the efficacy of a gelatin stent (XEN 45 Gel Stent; Allergan) implant in advanced glaucoma eyes that have failed prior aqueous shunt implantation. Methods: We retrospectively reviewed 6 patients with refractory glaucoma, defined as persistently high IOP (> 21 mmHg) despite taking at least 3 IOP-lowering medications subsequent to undergoing a glaucoma drainage device (GDD) with or without a second GDD or cilioablative procedure. Eyes with previous failed GDD underwent subconjunctival 0.3 cc (0.4 mg/ml) mitomycin C, tenonectomy, and placement of an ab- externo XEN stent. The outcome measures included change in IOP and the number of glaucoma medications. Success was defined as patients achieving an IOP ≤ 18 mmHg with a percentage reduction of 25% or 15 mmHg and 40% mean IOP reduction from baseline while taking the same number or fewer medications. Results: All six eyes with age of 77.6 ± 7.82 years who underwent XEN implantation following previous GDD surgery had primary open-angle glaucoma. The IOP decreased significantly from 32.33 ± 5.99 to 12.67 ± 3.27 mmHg (p < 0.001) with a follow-up of 13.9 ± 2 (11.7–16.7) months. Visual acuity and visual field remained stable after XEN placement. Compared to the baseline number of medications of 4.2 ± 0.8, all medication was discontinued except in one eye on two drops at the end of the follow-up. The overall surgical success rate was 100%. No complications, needling, or additional procedures were required. Conclusion: This study described successful implantation of the XEN stent following failed GDD. XEN Gel stent implantation associated with mitomycin C and tenonectomy can be considered a viable surgical option for patients with a history of previously failed tube shunt requiring further IOP lowering. [ABSTRACT FROM AUTHOR]

Background: This study aimed to identify novel therapeutic targets for primary open-angle glaucoma (POAG). Methods: The summary-data-based Mendelian randomization (SMR) method was used to evaluate the genetic association between plasma proteins and POAG. Two sets of plasma protein quantitative trait loci (pQTLs) data considered exposures were obtained from the Icelandic Decoding Genetics Study and UK Biobank Pharma Proteomics Project. The summary-level genome-wide association studies data for POAG were extracted from the latest Round 10 release of the FinnGen consortium (8,530 cases and 391,275 controls) and the UK Biobank (4,737 cases and 458,196 controls). Colocalization analysis was used to screen out pQTLs that share the same variant with POAG as drug targets identified. The two-sample Mendelian randomization, reverse causality testing and phenotype scanning were performed to further validate the main findings. Protein-protein interaction, pathway enrichment analysis and druggability assessment were conducted to determine whether the identified plasma proteins have potential as drug targets. Results: After systematic analysis, this study identified eight circulating proteins as potential therapeutic targets for POAG. Three causal proteins with strong evidence of colocalization, ROBO1 (OR = 1.38, p = 1.48 x 10-4, PPH4 = 0.865), FOXO3 (OR = 0.35, p = 4.34 x 10-3, PPH4 = 0.796), ITIH3 (OR = 0.89, p = 2.76 x 10-4, PPH4 = 0.767), were considered tier one targets. Five proteins with medium support evidence of colocalization, NCR1 (OR = 1.25, p = 4.18 x 10-4, PPH4 = 0.682), NID1 (OR = 1.38, p = 1.54 x 10-3, PPH4 = 0.664), TIMP3 (OR = 0.91, p = 4.01 x 10-5, PPH4 = 0.659), SERPINF1 (OR = 0.81, p = 2.77 x 10-4, PPH4 = 0.59), OXT (OR = 1.17, p = 9.51 x 10-4, PPH4 = 0.526), were classified as tier two targets. Additional sensitivity analyses further validated the robustness and directionality of these findings. According to druggability assessment, Pimagedine, Resveratrol, Syringaresinol and Clozapine may potentially be important in the development of new anti-glaucoma agents. Conclusion: Our integrated study identified eight potential associated proteins for POAG. These proteins play important roles in neuroprotection, extracellular matrix regulation and oxidative stress. Therefore, they have promising potential as therapeutic targets to combat POAG. [ABSTRACT FROM AUTHOR]

Purpose: We evaluated the IOP-lowering efficacy and safety of latanoprostene bunod (LBN) ophthalmic solution 0.024% (Vyzulta®), the first topical nitric oxide-donating prostaglandin analog (PGA), in clinical practice. Materials and methods: A retrospective medical chart review from July 2021 to July 2023 of patients with open-angle glaucoma receiving LBN with at least 1 year follow–up was conducted. All included patients received LBN 0.024% as a replacement for a PGA, with examinations at 1-, 3-, 6-and 12-months follow-up. Main outcome measures were IOP, retinal nerve fiber layer thickness, visual fields before/after LBN use and adverse effects. Subgroup analysis with glaucoma types and PGA use were performed for additional IOP reduction after LBN use. Results: Among 78 included patients, 47 patients (81 eyes), 60% with open-angle glaucoma (OAG) remained on LBN throughout 12-month follow-up. Baseline IOP was 18.2±4.2 mm Hg, and Prostaglandin analog (PGA)-IOP was 14.4 ± 3.0 mm Hg (21% mean IOP reduction). After switched to LBN, mean additional IOP reduction was 1.0 mm Hg at month 1, and the greatest reduction was 1.6 mm Hg (8.8% additional mean IOP reduction) at month 12 (P<0.0001). Subgroup analysis (NTG, 73%) showed that mean additional IOP reduction at month 12 was 1.3±2.0 mm Hg in NTG group and 2.1±3.2 mm Hg in POAG group (7.7% vs. 8.7% additional IOP reduction rates, P = 0.23). Subgroup analysis of PGA use at month 12 was 1.8±2.3 mm Hg in tafluoprost group and 0.5±1.7 mm Hg in travoprost group (9.5% vs.2.6% additional IOP reduction rates, P = 0.02). Tolerable ocular adverse effects included irritation (n = 16, 19.8%), mild conjunctival hyperemia (n = 11, 13.6%), dark circles (n = 4, 4.9%) and blurred vision (n = 2, 2.5%). There were no significant visual field and retinal nerve fiber layer thickness changes after 12 months of treatment with LBN 0.024%. Conclusions: Although high intolerable adverse effects including conjunctival hyperemia and eye irritation happened in the first month, remaining sixty percent of patients exhibited statistically significant additional IOP reductions in the replacement of other PGAs during 12 months of clinical use of LBN 0.024%. [ABSTRACT FROM AUTHOR]

PurposeMaterials and methodsParameters measuredResultsConclusionsMetaplasia, chronic inflammation and subconjunctival fibrosis favor failure of bleb-dependent glaucoma surgery. The aim of the study is to identify the patients at a higher risk of post-surgical failure.Prospective, open study, performed in the Glaucoma Unit of the Hospital Universitario Virgen Macarena, from April to November 2021, with a minimum follow-up of one year. 38 eyes with ocular hypertension or chronic open-angle glaucoma were included. All patients underwent preoperative conjunctival sampling in the operating room, under topical or locoregional anesthesia.Sex, age, and laterality; number, type and mean time of preoperative drugs use; type of surgery performed; cytology results and degree of metaplasia; percentage of patients in whom the bleb was closed. Evaluation of potential correlation between bleb closure and any of the other variables.20 women and 18 men participated, with a mean age of 67 years. The mean number of preoperative hypotensive drugs was 2.7. The mean time of use was 90,97 +/- 48,97 months. Most patients had normal cytology, 8% had inflammatory infiltrate and 21% had squamous metaplasia. When relating bleb failure and cytology, we saw that in those who failed surgery, more than half had cytological alterations. A multiple logistic regression was performed, in which we observed that there was statistically significant association (p = .02) between surgical closure and altered cytology.According to these results, preoperative conjunctival cytology can help predict those cases with a lower probability of surgical success. [ABSTRACT FROM AUTHOR]

PurposeMethodsResultsConclusionTo systematically assess the association between cigarette smoking and development of Primary Open Angle Glaucoma (POAG) in the general adult population. Heterogeneity will be explored appropriately.Outcomes of glaucoma, OAG and POAG were explored in adults who were current, former, and never cigarette smokers. An additional category of ‘smokers with “any” smoking status’ was used where former smokers were not clearly distinguished from current and never smokers and in smokers whose form of smoking was not defined. All studies were observational and there was no limit to time period. Databases used were MEDLINE, Embase, Global Health and Web of Science. Study quality was assessed using the JBI critical appraisal tool. The DerSimonian-Laird random-effects model and weighting method was applied for meta-analysis with subgroup and sensitivity analyses along with meta-regression.Four cohort, six cross-sectional and nine case–control studies were included. Only one cohort study attained a low risk of bias (RoB), two cohort studies were of medium RoB and the rest of the studies were of high RoB. There was no evidence for an association between smoking statuses: current smoking: OR 0.96, 95%CI (0.76,1.21), former smoking: OR 0.96, 95%CI (0.83,1.11), smoking (any): OR 1.48, 95%CI (0.96, 2.29) and glaucoma. Sensitivity analyses did not have a material impact on findings. Heterogeneity was not explained by smoking status, study quality, smoking exposure, and glaucoma outcome criteria.This review suggests no evidence for an association between cigarette smoking and the development of POAG. There was no evidence that current, former, and general smoking increased the risk of glaucoma. [ABSTRACT FROM AUTHOR]

Purpose Setting Design Methods Results Conclusions To report the 2‐year efficacy and safety of penetrating canaloplasty versus ab externo canaloplasty for the treatment of primary open‐angle glaucoma (POAG).A single surgical site in China.This was a prospective, randomized controlled trial. POAG patients were randomly assigned to the penetrating canaloplasty or ab externo canaloplasty group.This study enrolled POAG patients who underwent penetrating canaloplasty or ab externo canaloplasty randomly. Surgical success, intraocular pressure (IOP), number of glaucoma medications, and surgical complications were evaluated until 24 months post‐operatively. Surgical success was defined as 6 mmHg ≤ IOP ≤21 mmHg with an IOP reduction ≥20%, which included qualified success (with or without medications) and complete success (without medications).A total of 52 eyes (45 patients) were randomly assigned to one of two groups: the penetrating canaloplasty group (PCP, n = 26) or the ab externo canaloplasty group (CP, n = 26). The probabilities of qualified success and complete success were 92.3% and 76.9%, respectively, in the PCP group and 64.1% and 52.1%, respectively, in the CP group at 24 months (p = 0.013, p = 0.042, log‐rank test). The mean IOP decreased from 30.8 ± 10.7 and 28.6 ± 11.8 mmHg to 14.1 ± 3.3 mmHg in the PCP group and 22.1 ± 13.6 mmHg in the CP group at year two (p = 0.007). The PCP group also received fewer medications (0.2 ± 0.5) than did the CP group (0.7 ± 1.2) at year two (p = 0.038). Post‐operative complications were similar, and the most common complications were transient IOP elevation and hyphema in the PCP group (42.3%, 46.2%) and the CP group (38.5%, 23.1%) (p > 0.05).Compared to ab externo canaloplasty, penetrating canaloplasty had a greater surgical success rate and better IOP reduction with a comparable rate of complications. [ABSTRACT FROM AUTHOR]

PurposeMethodsResultsConclusionTo identify prevalence of and risk factors for loss to follow up (LTFU) among a national cohort of patients with primary open-angle glaucoma (POAG).This retrospective cohort study analyzed data from the IRIS® Registry (Intelligent Research in Sight) database from 2014 through 2019 to assess LTFU among adult patients with POAG. POAG patients with at least one clinical encounter in 2014 were included. LTFU was defined as exceeding one year without a clinical encounter during the study period.Among 553,663 glaucoma patients, 277,019 (50%) became LTFU, of whom 184,548 (67%) never returned to care and 92,471 (33%) re-established follow-up after a lapse. Risk of LTFU was greatest among those younger than 60 years (RR = 1.38; 95% CI: 1.36–1.39) or older than 80 years (RR = 1.39; 95% CI: 1.38–1.40) compared to those in their 60s. Compared to White race, risk for LTFU was highest among Native Hawaiian/Pacific Islander (RR = 1.24; 95% CI: 1.17–1.31), Hispanic ethnicity (RR = 1.19; 95% CI: 1.18–1.20), and Black race (RR = 1.10; 95% CI: 1.09–1.11). Medicare insurance was associated with lower risk of LTFU (RR = 0.79; 95% CI: 0.78–0.79), whereas unknown/missing/no insurance was associated with greater risk (RR = 1.33; 95% CI: 1.32–1.34), compared to private insurance. Compared to mild-stage POAG, risk of LTFU was higher for moderate-stage (RR = 1.10; 95% CI: 1.08–1.13) and severe-stage disease (RR = 1.35; 95% CI: 1.32–1.38).We found a 50% prevalence of LTFU among POAG patients in the IRIS Registry over a 6-year study period, with greater risk among minority groups and those with more advanced disease. [ABSTRACT FROM AUTHOR]

Primary open-angle glaucoma (POAG) is subdivided depending on eye pressure. Patients with normal-tension glaucoma (NTG) have never had high intraocular pressure (IOP) measured while patients with ocular hypertension (OHT) have high eye pressure but no signs of glaucoma. Although IOP is considered to be a risk factor for all glaucoma patients, it is reasonable to assume that other risk factors such as inflammation play a role. We aimed to characterize the proteome and cytokine profile during hypoxia in plasma from patients with NTG (n = 10), OHT (n = 10), and controls (n = 10). Participants were exposed to hypoxia for two hours, followed by 30 min of normoxia. Samples were taken before ("baseline"), during ("hypoxia"), and after hypoxia ("recovery"). Proteomics based on liquid chromatography coupled with mass spectrometry (LC–MS) was performed. Cytokines were measured by Luminex assays. Bioinformatic analyses indicated the involvement of complement and coagulation cascades in NTG and OHT. Regulation of high-density lipoprotein 3 (HDL3) apolipoproteins suggested that changes in cholesterol metabolism are related to OHT. Hypoxia decreased the level of tumor necrosis factor-α (TNF-α) in OHT patients compared to controls. Circulating levels of interleukin-1β (IL-1β) and C-reactive protein (CRP) were decreased in NTG patients compared to controls during hypoxia. After recovery, plasma interleukin-6 (IL-6) was upregulated in patients with NTG and OHT. Current results indicate an enhanced systemic immune response in patients with NTG and OHT, which correlates with pathogenic events in glaucoma. Apolipoproteins may have anti-inflammatory effects, enabling OHT patients to withstand inflammation and development of glaucoma despite high IOP. [ABSTRACT FROM AUTHOR]

Background: To report the surgical safety of reinforced bio-interventional cyclodialysis with scleral allograft reinforcement. Methods: This was a consecutive case series of 243 eyes with open-angle glaucoma who underwent a bio-scaffolded cyclodialysis (BSC) procedure for uveoscleral outflow enhancement using allogeneic bio-spacers to maintain patency of the internal filtration conduit. Results: 79% of the eyes underwent concomitant phacoemulsification cataract surgery prior to BSC intervention, while the remaining eyes underwent stand-alone BSC surgery. All patients had a postoperative surgical safety period of at least 30 days. There were no sight-threatening or serious ocular adverse events. There was one case of prolonged iritis beyond 30 days, which resolved with topical treatment. Two cases (0.8%) of intraoperative and five (2%) of postoperative non-sight-threatening hyphema were without clinical sequelae, which resolved with conservative management. There were 11 cases of IOP elevation and one case of numeric hypotony without maculopathy, which resolved within the study period. The rate of secondary surgical intervention for IOP control was low, and overall, IOP for the cohort improved in the postoperative period, with 78.6% of eyes achieving IOP ≤ 18 mmHg without an increase in medications. Conclusions: Allogeneic biotissue for cyclodialysis intervention demonstrates a biocompatible ocular profile as an implantable material for internal scleral reinforcement during uveoscleral outflow enhancement surgery. [ABSTRACT FROM AUTHOR]

Background: Age-related eye diseases (AREDs) have become increasingly prevalent with the aging population, serving as the leading causes of visual impairment worldwide. Epigenetic clocks are generated based on DNA methylation (DNAm) levels and are considered one of the most promising predictors of biological age. This study aimed to investigate the bidirectional causal association between epigenetic clocks and common AREDs or glaucoma endophenotypes. Methods: Instrumental variables for epigenetic clocks, AREDs, and glaucoma endophenotypes were obtained from corresponding genome-wide association study data of European descent. Bidirectional two-sample Mendelian randomization (MR) was employed to explore the causal relationship between epigenetic clocks and AREDs or glaucoma endophenotypes. Multivariable MR (MVMR) was used to determine whether glaucoma endophenotypes mediated the association of epigenetic clocks with glaucoma. Multiple sensitivity analyses were conducted to confirm the robustness of MR estimates. Results: The results showed that an increased intrinsic epigenetic age acceleration (HorvathAge) was significantly associated with an increased risk of primary open-angle glaucoma (OR = 1.04, 95% CI 1.02 to 1.06, P = 6.1E−04). The epigenetic age acceleration (EEA) of HannumAge was related to a decreased risk of primary angle-closure glaucoma (OR = 0.92, 95% CI 0.86 to 0.99, P = 0.035). Reverse MR analysis showed that age-related cataract was linked to decreased HannumAge (β = −0.190 year, 95% CI −0.374 to −0.008, P = 0.041). The EEA of HannumAge (β = −0.85 μm, 95% CI −1.57 to −0.14, P = 0.019) and HorvathAge (β = −0.63 μm, 95% CI −1.18 to −0.08, P = 0.024) were associated with decreased central corneal thickness (CCT). PhenoAge was related to an increased retinal nerve fiber layer thickness (β = 0.06 μm, 95% CI 0.01 to 0.11, P = 0.027). MVMR analysis found no mediation effect of CCT in the association of HannumAge and HorvathAge with glaucoma. DNAm-based granulocyte proportions were significantly associated with presbyopia, rhegmatogenous retinal detachment, and intraocular pressure (P < 0.05). DNAm-based plasminogen activator inhibitor-1 levels were significantly related to age-related macular degeneration and intraocular pressure (P < 0.05). Conclusion: The present study revealed a causal association between epigenetic clocks and AREDs. More research is warranted to clarify the potential mechanisms of the biological aging process in AREDs. [ABSTRACT FROM AUTHOR]

Simple Summary: Ovarian cancer is a prevalent gynecological cancer and a leading cause of cancer-associated mortality worldwide. Ovarian cancer is related to several oxidative stress-related diseases. Open-angle glaucoma (OAG) is a neurodegenerative disease that is associated with elevated oxidative stress, while the relationship between OAG and ovarian cancer is vague. Consequently, we aim to survey the interrelationship between ovarian cancer and OAG. In this retrospective cohort study, people with ovarian cancer were recruited and age-matched with a 1:4 ratio of non-ovarian to cancer. The multivariable analysis exhibited a higher incidence of OAG in the ovarian cancer group than the non-ovarian cancer patients, which was more prominent in those older than 60 years and with ovarian cancer for longer than two years. Thus, the presence of ovarian cancer is associated with a higher possibility of later OAG. Routine glaucoma exams could be recommended for women diagnosed with ovarian cancer for longer than 2 years or who are older than 60. We aim to explore the possible association between ovarian cancer and the subsequent development of open-angle glaucoma (OAG) using the Taiwan Longitudinal Health Insurance Database (LHID) 2000. A retrospective cohort study was executed, and individuals with ovarian cancer were enrolled and age-matched (with a 1:4 ratio) to non-ovarian cancer individuals. A total of 4990 and 19,960 patients were put into the ovarian cancer and control groups. The main outcome was the presence of OAG according to the LHID 2000 codes. The Cox proportional hazard regression was adopted to demonstrate the adjusted hazard ratio (aHR) and 95% confidence interval (CI) of OAG between the ovarian cancer and control groups. There were a total of 241 and 1029 OAG cases observed in the ovarian cancer group and the control group, respectively. The incidence of OAG was significantly higher in the ovarian cancer group than in the control group according to multivariable analysis (aHR: 1.18, 95% CI: 1.02–1.37, p = 0.022). The ovarian cancer patients older than 60 years showed a significantly higher risk of OAG compared to the non-ovarian cancer individuals of the same age (aHR: 1.39, 95% CI: 1.16–1.63, p = 0.001). Additionally, ovarian cancer individuals with a disease interval of more than two years presented a significantly higher incidence of OAG than the non-ovarian cancer group (p < 0.05). In conclusion, ovarian cancer positively correlates with a high rate of subsequent OAG, especially in elderly persons with a long disease interval. [ABSTRACT FROM AUTHOR]

Nebivolol hydrochloride (NEB), a 3rd-generation beta-blocker, was recently explored in managing open-angle glaucoma due to its mechanism of action involving nitric oxide release for the vasodilation. To overcome the issue of low ocular bioavailability and the systemic side effects associated with conventional ocular formulation (aqueous suspension), we designed and optimized polycaprolactone polymeric nanoparticles (NEB-PNPs) by applying design of experiments (DoE). The particle size and drug loading of the optimized NEB-PNPs were 270.9 ± 6.3 nm and 28.8 ± 2.4%, respectively. The optimized NEB-PNPs were suspended in a dual-sensitive in situ gel prepared using a mixture of P407 + P188 (as a thermo-sensitive polymer) and κCRG (as an ion-sensitive polymer), reported previously by our group. The NEB-PNPs-loaded in situ gel (NEB-PNPs-ISG) formulation was characterized for its rheological behavior, physical and chemical stability, in vitro drug release, and in vivo efficacy. The NEB-PNPs-loaded in situ gel, in ocular pharmacokinetic studies, achieved higher aqueous humor exposure (AUC0–t = 329.2 ng × h/mL) and for longer duration (mean residence time = 9.7 h) than compared to the aqueous suspension of plain NEB (AUC0–t = 189 ng × h/mL and mean residence time = 6.1 h) reported from our previous work. The pharmacokinetic performance of NEB-PNPs-loaded in situ gel translated into a pharmacodynamic response with 5-fold increase in the overall percent reduction in intraocular pressure by the formulation compared to the aqueous suspension of plain NEB reported from our previous work. Further, the mean response time of NEB-PNPs-loaded in situ gel (12.4 ± 0.6 h) was three times higher than aqueous suspension of plain NEB (4.06 ± 0.3 h). [ABSTRACT FROM AUTHOR]

PurposesMethodsResultsConclusionsTo determine the relationship between carotid artery stenosis (CAS) and the development of open-angle glaucoma (OAG) in the Taiwanese population.This retrospective cohort study was conducted using Chang Gung Research Database. Cox-proportional hazards model was applied to calculate the hazard ratio for OAG between CAS and the control cohort.Among 19,590 CAS patients, 17,238 had mild CAS (<50%), 1,895 had moderate CAS (50–69%), and 457 had severe CAS (≥70%). The CAS cohort had a higher proportion of several comorbidities. After adjusting for comorbidities, no significant difference in OAG development was found between CAS and control cohorts. Matching for key comorbidities, no significant differences in OAG incidence were found between matched cohorts (P = .869). Subdividing the matched CAS cohort by stenosis severity: mild (<50%), moderate (50–69%), and severe (≥70%), a statistically significantly lower OAG risk was observed in patients with mild CAS stenosis (HR: 1.12, 95% CI = 1.03–1.21, P = .006). Kaplan-Meier analysis revealed reduced OAG incidence in CAS patients who underwent surgical intervention, compared to the control cohort (P <.001). Subgroup analysis revealed that patients in the mild CAS stenosis group, those who underwent surgical intervention exhibited a reduced OAG risk (HR: 0.29, 95% CI = 0.15–0.58, P = .001).No statistically significant differences in OAG risk were observed between patients with CAS and the control cohort. The severity of CAS appears to influence OAG risk, with surgical intervention potentially offering protective effects, particularly in patients with mild CAS stenosis (<50%), suggesting that enhanced ocular perfusion post-surgery may act as a protective factor against OAG development. [ABSTRACT FROM AUTHOR]