Widefield swept-source optical coherence tomography angiography metrics associated with neovascular glaucoma in patients with proliferative diabetic retinopathy.

PURPOSE: To explore the association between widefield swept-source optical coherence tomography angiography (WF SS-OCTA) metrics, including nonperfusion area (NPA) and neovascularization (NV), and presence of neovascular glaucoma (NVG) in patients with proliferative diabetic retinopathy (PDR). METHODS: A prospective, cross-sectional study was conducted from November 2018 to February 2020. A total of 85 eyes of 60 PDR patients without NVG and 9 eyes of 8 PDR patients with NVG were included. Retinal ischemic parameters (NPA; ischemia index [NPA/total retinal area]) and NV features (NV number; NV area; NV vessel density) were evaluated. Foveal avascular zone (FAZ), macular thickness/volume, and choroidal thickness/volume were obtained using the Zeiss ARI Network. WF SS-OCTA retinal and choroidal metrics, systemic, and ocular parameters were screened using Least Absolute Shrinkage and Selection Operator (LASSO) logistic regression for variable selection. Firth's bias-reduced logistic regression (outcome: presence of NVG) was subsequently used to identify parameters associated with NVG. RESULTS: After LASSO variable selection, 8 variables were significantly associated with the presence of NVG: DM duration (years), insulin (yes/no), best-corrected visual acuity (BCVA) (logMAR), IOP, ischemia index, skeletonized vessel density, macular thickness (inner inferior, outer temporal regions). Firth's bias-reduced logistic regression showed ischemia index (odds ratio [OR]=13.2, 95% confidence interval [CI]:5.3-30.7, P<0.001) and BCVA (OR=5.8, 95%CI:1.2-28.8, P<0.05) were associated with the presence of NVG. NV metrics, FAZ, and choroidal parameters were not related to NVG. CONCLUSIONS: Retinal ischemia but not NV was associated with the presence of NVG in patients with PDR using WF SS-OCTA. Larger, longitudinal studies are needed to validate imaging biomarkers associated with diabetic NVG.

Prevalence of venous loops and association with retinal ischemia in diabetic retinopathy using widefield swept-source OCT angiography.

PURPOSE: To investigate the prevalence and clinical characteristics of diabetic patients with retinal venous loops (RVLs) and to assess the association with retinal ischemia using widefield swept-source optical coherence tomography angiography (WF SS-OCTA). METHODS: In this retrospective, cross-sectional study, a total of 195 eyes of 132 diabetic patients (31 eyes with no diabetic retinopathy (DR), 76 eyes with nonproliferative DR (NPDR), and 88 eyes with proliferative DR (PDR)) were imaged with WF SS-OCTA using Angio 6 × 6 mm and Montage 15 × 15 mm scans. Quantitative ischemia-related parameters, including ischemia index (ratio of nonperfusion area to total retinal area), foveal avascular zone (FAZ), and neovascularization features, were evaluated. RVLs were classified as type I or type II according to the branching level of the feeder vessel. A multivariate generalized estimating equations (GEE) logistic regression model was used to analyze the association of systemic parameters and ischemia-related metrics with RVLs in PDR eyes. RESULTS: Forty-eight RVLs were identified in 22 eyes (11.28%). The prevalence of RVLs was higher in PDR compared to NPDR eyes (21.59% vs. 3.95%, P < 0.05). Type II RVLs accounted for a higher proportion than type I (89.58% vs. 10.42%, P < 0.001). RVLs were more likely to originate from superior (vs. inferior) and temporal (vs. nasal) veins (P < 0.05). The GEE model showed that neovascularization (NV) flow area and diastolic blood pressure were associated with RVLs in the PDR group (P < 0.05). CONCLUSION: WF SS-OCTA is useful for the identification of RVLs in patients with DR. NV flow area and diastolic blood pressure were associated with the presence of RVLs in eyes with PDR. Ischemia index, FAZ, and other WF SS-OCTA parameters were not associated with RVLs. Further longitudinal studies are needed to identify the role of RVLs in DR progression.

Structure-function associations between contrast sensitivity and widefield swept-source optical coherence tomography angiography in diabetic macular edema.

PURPOSE: To evaluate the relationship between contrast sensitivity (CS) and widefield swept-source optical coherence tomography angiography (WF SS-OCTA) vascular metrics in diabetic macular edema (DME) was the purpose. METHODS: This prospectively enrolled cross-sectional observational study included 61 eyes of 48 patients that were tested with the quantitative CS function (qCSF) test on the same day as imaging with WF SS-OCTA (PLEX® Elite 9000, Carl Zeiss Meditec) 3 × 3, 6 × 6, and 12 × 12 mm scans. Outcomes included visual acuity (VA) and multiple qCSF metrics. Vascular metrics included vessel density (VD) and vessel skeletonized density (VSD) in the superficial (SCP) and deep capillary plexus (DCP) and whole retina (WR) and foveal avascular zone (FAZ) parameters. Mixed effects multivariable linear regression models controlling for age, lens status, and diabetic retinopathy stage were performed. Standardized beta coefficients were calculated by refitting the standardized data. RESULTS: SS-OCTA metrics had a significant association with CS and VA. The effect size of OCTA metrics was larger on CS compared to VA. For example, the standardized beta coefficients for VSD and CS at 3 cpd (ßSCP = 0.76, ßDCP = 0.71, ßWR = 0.72, p < 0.001) were larger than those for VA (ßSCP = - 0.55, p < 0.001; ßDCP = - 0.43, p = 0.004; ßWR = - 0.50, p < 0.001). On 6 × 6 mm images, AULCSF, CS at 3 cpd, and CS at 6 cpd were significantly associated with VD and VSD in all three slab types (SCP, DCP, and WR), while VA was not. CONCLUSION: Structure-function associations in patients with DME leveraging the qCSF device suggest microvascular changes on WF SS-OCTA are associated with larger changes in contrast sensitivity than VA.

DCAF13 promotes pluripotency by negatively regulating SUV39H1 stability during early embryonic development.

Mammalian oocytes and zygotes have the unique ability to reprogram a somatic cell nucleus into a totipotent state. SUV39H1/2-mediated histone H3 lysine-9 trimethylation (H3K9me3) is a major barrier to efficient reprogramming. How SUV39H1/2 activities are regulated in early embryos and during generation of induced pluripotent stem cells (iPSCs) remains unclear. Since expression of the CRL4 E3 ubiquitin ligase in oocytes is crucial for female fertility, we analyzed putative CRL4 adaptors (DCAFs) and identified DCAF13 as a novel CRL4 adaptor that is essential for preimplantation embryonic development. Dcaf13 is expressed from eight-cell to morula stages in both murine and human embryos, and Dcaf13 knockout in mice causes preimplantation-stage mortality. Dcaf13 knockout embryos are arrested at the eight- to sixteen-cell stage before compaction, and this arrest is accompanied by high levels of H3K9me3. Mechanistically, CRL4-DCAF13 targets SUV39H1 for polyubiquitination and proteasomal degradation and therefore facilitates H3K9me3 removal and zygotic gene expression. Taken together, CRL4-DCAF13-mediated SUV39H1 degradation is an essential step for progressive genome reprogramming during preimplantation embryonic development.

Widefield Swept-Source OCT Angiography Metrics Associated with the Development of Diabetic Vitreous Hemorrhage: A Prospective Study.

PURPOSE: To investigate the association among widefield swept-source (SS) OCT angiography (OCTA) metrics and systemic parameters and vitreous hemorrhage (VH) occurrence in eyes with proliferative diabetic retinopathy (PDR). DESIGN: Prospective, observational study. PARTICIPANTS: Fifty-five eyes from 45 adults with PDR, with no history of VH, followed up for at least 3 months. METHODS: All patients underwent widefield SS OCTA (Montage 15 × 15 mm and high-definition (HD)-51 line scan) imaging. Images were evaluated independently by 2 graders for quantitative and qualitative widefield SS OCTA metrics defined a priori. Systemic and ocular parameters and widefield SS OCTA metrics were screened using least absolute shrinkage and selection operator and logistic or Cox regression for variable selection. Firth's bias-reduced logistic regression models (outcome, occurrence of VH) and Cox regression models (outcome, time to occurrence of VH) were used to identify parameters associated with VH occurrence. MAIN OUTCOME MEASURES: Occurrence of VH. RESULTS: Over a median follow-up of 363 days (range, 28-710 days), 13 of 55 PDR eyes (24%) demonstrated VH during the follow-up period. Presence of extensive neovascularizations (odds ratio, 8.05; 95% confidence interval [CI], 1.43-58.56; P = 0.02), defined as neovascularizations with total area of more than 4 disc diameters, and forward neovascularizations (odds ratio, 5.42; 95% CI, 1.26-35.16; P = 0.02) that traversed the posterior hyaloid face into the vitreous were associated with the occurrence of VH. The presence of flat neovascularizations (odds ratio, 0.25; 95% CI, 0.04-1.01; P = 0.05) confined to the posterior hyaloid face was associated with a lower risk of VH with borderline significance. Similarly, presence of extensive neovascularizations (hazard ratio, 18.24; 95% CI, 3.51-119.47; P < 0.001) and forward neovascularizations (hazard ratio, 9.60; 95% CI, 2.07-68.08; P = 0.002) was associated significantly with time to development of VH. CONCLUSIONS: Widefield SS OCTA is useful for evaluating neovascularizations and their relationship with the vitreous. The presence of forward and extensive neovascularizations was associated with the occurrence of VH in patients with PDR. Larger samples and longer follow-up are needed to verify the risk factors and imaging biomarkers for diabetic VH.

Isoliquiritigenin protects against angiotensin II-induced fibrogenesis by inhibiting NF-κB/PPARγ inflammatory pathway in human Tenon's capsule fibroblasts.

PURPOSE: To examine the protective effects of Isoliquiritigenin (ISL) in angiotensin II (ANG II)-induced inflammation and fibrosis on Human Tenon's capsule Fibroblasts (HTFs) and Mouse Peritoneal Macrophages (MPMs). This study also investigated the potential mechanism of action of ISL. METHOD: Methyl-thiazolyl tetrazolium (MTT) assay was used to test ISL toxicity. An ELISA and an RT-qPCR assay detected the inflammatory cytokines (TNF-α, IL-6, COX-2, and ICAM-1). A Western blot investigated the expression levels of inflammation-related signals [nuclear factor-κB (NF-κB), peroxisome proliferator-activated receptor γ (PPARγ)], and fibrogenesis, including fibronectin and alpha-smooth muscle actin (α-SMA)]. Protein expressions of α-SMA were measured by immunofluorescence. RESULTS: Pre-treatment with ISL (10 or 20 µM) dose-dependently decreased the mRNA levels of TNF-α, IL-6, ICAM-1, and COX-2 induced by ANG II (1 µg/ml) in both MPMs and HTFs. ANG II remarkably increased the amount of P65 in the nuclei and decreased the amount of P65 in the cytoplasm. Additionally, ANG II reduced PPARγ expression levels in a time-dependent manner. Furthermore, these effects which were induced by ISL were remarkably neutralized by ISL pre-treatment. Finally, ANG II markedly elevated the expression of fibronectin and α-SMA. CONCLUSION: ISL could alleviate ANG II-induced fibrogenesis by inhibiting the NF-κB/PPARγ inflammatory pathway. In addition, ISL may be a potential agent for the treatment of conjunctival fibrosis. Most importantly, the NF-κB/PPARγ signaling pathway could be an effective therapeutic target for the prevention and treatment of conjunctival fibrosis after glaucoma surgery.

Isoliquiritigenin protects against sepsis-induced lung and liver injury by reducing inflammatory responses.

Sepsis, one of the most fatal diseases worldwide, often leads to multiple organ failure, mainly due to uncontrolled inflammatory responses. Despite accumulating knowledge obtained in recent years, effective drugs to treat sepsis in the clinic are still urgently needed. Isoliquiritigenin (ISL), a chalcone compound, has been reported to exert anti-inflammatory properties. However, little is known about the effects of ISL on sepsis and its related complications. In this study, we investigated the potential protective effects of ISL on lipopolysaccharide (LPS)-induced injuries and identified the mechanisms underlying these effects. ISL inhibited inflammatory cytokine expression in mouse primary peritoneal macrophages (MPMs) exposed to LPS. In an acute lung injury (ALI) mouse model, ISL prevented LPS-induced structural damage and inflammatory cell infiltration. Additionally, pretreatment with ISL attenuated sepsis-induced lung and liver injury, accompanied by a reduction in inflammatory responses. Moreover, these protective effects were mediated by the nuclear factor kappa B (NF-κB) pathway-mediated inhibition of inflammatory responses in vitro and in vivo. Our study suggests that ISL may be a potential therapeutic agent for sepsis-induced injuries.

Anterior chamber proliferative membrane interception (AC-PMI)-enhanced trabeculectomy versus trabeculectomy for treating neovascular glaucoma: protocol for a randomized controlled trial.

BACKGROUND: Neovascular glaucoma (NVG) is an irreversible blinding eye disease worldwide and is classified as one of the refractory glaucoma conditions, severely impacting visual function and vision. Unfortunately, effective surgical interventions to improve the prognosis of NVG patients are currently lacking. The study aims to evaluate the efficacy and safety of anterior chamber proliferative membrane interception (AC-PMI)-enhanced trabeculectomy compared to the traditional trabeculectomy. METHODS: AC-PMI enhanced trabeculectomy versus trabeculectomy for the treatment of NVG is a single-center, prospective, double-arms, and randomized controlled trial of superior efficacy, which will involve 100 NVG inpatients. Patients will be randomly assigned into two groups using the random number table method. One group will undergo trabeculectomy using anti-vascular endothelial growth factor (Anti-VEGF) preoperatively and mitomycin C intraoperatively, while the other group will undergo AC-PMI enhanced trabeculectomy with the same medications (Anti-VEGF and mitomycin C). The patients will be followed up at the baseline and 1 day, 1 week, 1 month, 3 months, 6 months, 12 months, 18 months, and 24 months postoperatively. Meanwhile, we will collect the demographics, characteristics, and examination results and monitor any occurrences of adverse events at each follow-up time. DISCUSSION: This is an efficacy study of a novel surgical approach for treating neovascular glaucoma. Building upon conventional filtering surgeries, this approach introduces an additional step involving the interception of the proliferative membrane to effectively halt the growth of fibrovascular tissue. This study aims to explore a promising new surgical approach for managing NVG and contribute to the advancement of glaucoma treatment strategies. TRIAL REGISTRATION: ChiCTR ChiCTR2200055138. Registered on 01 January 2022. https://www.chictr.org.cn/showproj.html?proj=145255.

Acute angle-closure glaucoma before, during, and after the outbreak of COVID-19 in China.

Objectives: Acute angle-closure glaucoma (AACG) is a major cause of irreversible and severe visual function loss. Robust rise in AACG was observed in the ophthalmic outpatient clinics concomitant with the outbreak of COVID-19 infection in China after the relaxing of "zero-COVID policy" in early December 2022. Here we compared the demographic and clinical profiles of patients with AACG before, during and after the COVID-19 outbreak. Underlying mechanisms were tentatively investigated. Methods: This is a retrospective comparative study. Consecutive cases with newly diagnosed AACGs in a tertiary eye hospital were retrospectively collected during December 17, 2022 to January 8, 2023. Data from the same period in 2018-2019 and 2019-2020, 2020-2021 and 2021-2022, and 2023-2024 were collected as pre-pandemic, pandemic-control, and post-pandemic control, respectively. For the patients in 2022-2023 outbreak group, COVID-19 infection was confirmed by reversed transcriptase-polymerase chain reaction or antibody test for severe acute respiratory syndrome coronavirus disease 2 (SARS-CoV-2) from nasopharyngeal swabs. Ocular parameters, serum electrolytes and coagulative parameters were compared between COVID-19 positive and negative AACGs in observational group. SARS-CoV-2 nucleic acid in the aqueous humor was detected. Results: A total of 106 AACG cases were diagnosed during the outbreak period in 2022-2023. In contrast, 18 (in 2018-2019) and 22 (in 2019-2020) cases were included during pre-pandemic period, and 21 (in 2023-2024) during the post-pandemic period. Only 13 and 4 newly onset AACG were included in 2020-2021 and 2021-2022 during the pandemic-control period, respectively. Younger age and higher proportion of bilateral involvement were detected in COVID-19 outbreak group than that of other groups (p = 0.034 and p = 0.080). Sixty-eight (64.2 %) patients in the outbreak group had a confirmed COVID-19 infection. Intervals between infection and AACG attack was 52 ± 85h (0-15d). Fifty-three patients (77.9 %) reported the applications of ibuprofen or other antipyretic medications and 25 (36.8 %) reported large volume water intake before AACG attack. COVID-19-positive AACG patients had higher level of D-dimer than their negative counterparts (1.13 ± 2.60 mg/L vs. 0.46 ± 0.43 mg/L, p = 0.083). No difference in IOP, serum electrolytes, and coagulative parameters other than D-dimer was observed between COVID-19 positive and negative cases. SARS-CoV-2 were negative in the aqueous humor from 14 COVID-19 positive and 8 negative patients. Conclusion: COVID-19 infection surged the onset of AACG in patients at risk. Mental stress, water intake, increased choroidal thickness due to SARS-CoV-2 induced ACE receptor activation, and hyper-coagulation, may contribute to the disease onset. Ocular involvement should not be ignored in both routine and new systemic emergent conditions.

Efficacy and safety of penetrating canaloplasty versus ab externo canaloplasty for primary open-angle glaucoma: A randomized controlled trial.

PURPOSE: To report the 2-year efficacy and safety of penetrating canaloplasty versus ab externo canaloplasty for the treatment of primary open-angle glaucoma (POAG). SETTING: A single surgical site in China. DESIGN: This was a prospective, randomized controlled trial. POAG patients were randomly assigned to the penetrating canaloplasty or ab externo canaloplasty group. METHODS: 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). RESULTS: 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). CONCLUSIONS: Compared to ab externo canaloplasty, penetrating canaloplasty had a greater surgical success rate and better IOP reduction with a comparable rate of complications.

ISR inhibition reverses pancreatic ß-cell failure in Wolfram syndrome models.

Pancreatic ß-cell failure by WFS1 deficiency is manifested in individuals with wolfram syndrome (WS). The lack of a suitable human model in WS has impeded progress in the development of new treatments. Here, human pluripotent stem cell derived pancreatic islets (SC-islets) harboring WFS1 deficiency and mouse model of ß cell specific Wfs1 knockout were applied to model ß-cell failure in WS. We charted a high-resolution roadmap with single-cell RNA-seq (scRNA-seq) to investigate pathogenesis for WS ß-cell failure, revealing two distinct cellular fates along pseudotime trajectory: maturation and stress branches. WFS1 deficiency disrupted ß-cell fate trajectory toward maturation and directed it towards stress trajectory, ultimately leading to ß-cell failure. Notably, further investigation of the stress trajectory identified activated integrated stress response (ISR) as a crucial mechanism underlying WS ß-cell failure, characterized by aberrant eIF2 signaling in WFS1-deficient SC-islets, along with elevated expression of genes in regulating stress granule formation. Significantly, we demonstrated that ISRIB, an ISR inhibitor, efficiently reversed ß-cell failure in WFS1-deficient SC-islets. We further validated therapeutic efficacy in vivo with ß-cell specific Wfs1 knockout mice. Altogether, our study provides novel insights into WS pathogenesis and offers a strategy targeting ISR to treat WS diabetes.

RNA m6A modification regulates cell fate transition between pluripotent stem cells and 2-cell-like cells.

N6-methyladenosine (m6A) exerts essential roles in early embryos, especially in the maternal-to-zygotic transition stage. However, the landscape and roles of RNA m6A modification during the transition between pluripotent stem cells and 2-cell-like (2C-like) cells remain elusive. Here, we utilised ultralow-input RNA m6A immunoprecipitation to depict the dynamic picture of transcriptome-wide m6A modifications during 2C-like transitions. We found that RNA m6A modification was preferentially enriched in zygotic genome activation (ZGA) transcripts and MERVL with high expression levels in 2C-like cells. During the exit of the 2C-like state, m6A facilitated the silencing of ZGA genes and MERVL. Notably, inhibition of m6A methyltransferase METTL3 and m6A reader protein IGF2BP2 is capable of significantly delaying 2C-like state exit and expanding 2C-like cells population. Together, our study reveals the critical roles of RNA m6A modification in the transition between 2C-like and pluripotent states, facilitating the study of totipotency and cell fate decision in the future.

Outcomes of Penetrating Canaloplasty in Childhood Glaucoma.

PRCIS: Penetrating canaloplasty was safe and effective for the management of refractory childhood glaucoma. PURPOSE: The purpose of this paper is to report the safety and efficacy of penetrating canaloplasty for the management of childhood glaucoma. MATERIALS AND METHODS: This single-center prospective interventional case series enrolled 50 eyes of 32 patients with childhood glaucoma between July 2017 and July 2020. Penetrating canaloplasty to create direct communication between the anterior chamber and tensioning suture-dilated the Schlemm canal was performed through a trabecular meshwork ostium in the affected eyes. Preoperative and postoperative intraocular pressure (IOP), number of glaucoma medications, and procedure-related complications were recorded. Qualified and complete success was defined as IOP≥5 and ≤21 mm Hg with or without glaucoma medications, respectively. RESULTS: A total of 43 eyes (86.0%) achieved 360 degrees catheterization of Schlemm canal and completed penetrating canaloplasty. The median age at surgery was 5 years (range, 10 d-17 y, mean 6.20±5.46 y). The mean IOP decreased from 33.11±10.89 mm Hg on 2 medications (median, range: 0-5) before surgery to 13.46±4.71 mm Hg on 0 medications (median, range:0-2) postoperatively at 12 months ( P <0.001). Complete and qualified success rates were 81.08% and 89.19%, respectively, at the 12-month follow-up. Hyphema (6/43, 13.95%) and a transient shallow anterior chamber with hypotony (5/43, 11.63%) were the most commonly observed early complications. CONCLUSION: Penetrating canaloplasty demonstrated good safety and efficacy in eyes with childhood glaucoma, and may be considered an option for managing refractory childhood glaucoma.

Clinical outcomes of penetrating canaloplasty in patients with traumatic angle recession glaucoma: a prospective interventional case series.

BACKGROUND/AIM: To evaluate the clinical outcomes of penetrating canaloplasty in traumatic angle recession glaucoma at 1 year. METHODS: Patients with angle recession glaucoma underwent penetrating canaloplasty, a new Schlemm's canal-based internal drainage procedure, which creates a direct canal for flow of aqueous humour from the anterior chamber to the ostia of Schlemm's canal via a window created at the corneal scleral bed without use of antimetabolites. Postoperative intraocular pressure (IOP), number of glaucoma medications, and procedure-related complications were evaluated. Success was defined as an IOP ≤21 mm Hg without (complete) or with (qualified) use of glaucoma medication. RESULTS: Forty eyes in 40 patients with angle recession glaucoma underwent successful circumferential catheterisation. The mean patient age was 42±13 years. In patients with penetrating canaloplasty that was deemed to be completely successful, the mean IOP decreased from a preoperative value of 37.8±12.3 mm Hg on 3.3±1.2 anti-glaucoma medications to 18.5±6.4 mm Hg on 1.2±1.4 medications, 14.9±4.6 mm Hg on 0.1±0.5 medications, 15.7±5.4 mm Hg on 0.1±0.4 medications and 14.8±3.6 mm Hg on 0.1±0.5 medications at 1, 3, 6 and 12 months postoperatively (p<0.05). Complete success was achieved in 35/40 eyes (87.5%) at 6 months and in 34/38 (89.5%) at 12 months. Hyphema (18/40, 45.0%) and transient IOP elevation (≥30 mm Hg, 9/40, 22.5%) were the most common postoperative complications. CONCLUSION: Penetrating canaloplasty significantly reduces IOP and has a high success rate in angle recession glaucoma. TRIAL REGISTRATION NUMBER: ChiCTR1900020511.

Characterising collateral vessels in eyes with branch retinal vein occlusions using widefield swept-source optical coherence tomography angiography.

BACKGROUND/AIMS: To characterise the morphology, location and functional significance of both macular and extramacular collateral vessels (CVs) in patients with a history of branch retinal vein occlusion (BRVO) using widefield swept-source optical coherence tomography angiography (WF SS OCTA). METHODS: Patients with a history of BRVO underwent WF SS OCTA testing to acquire 12×12 mm images, which were evaluated for CVs and non-perfusion area (NPA). Region of interest analysis of individual CVs was performed to identify correlations between CV size, depth and retinal location. Mixed effects multivariate regression analyses of factors associated with NPA and visual acuity (VA) were performed. RESULTS: Fifty-five CVs were identified in 28 BRVO eyes from 27 patients. CVs were identified in 42.9% (12/28) of eyes with a history of BRVO, and of these, 45.5% (25/55) were extramacular. The majority of CVs (87.3%, 48/55) coursed through both the superficial and the deep capillary plexus (DCP), while a subset (12.7%, 7/55) were strictly superficial. No CVs were found to course strictly through the DCP alone. CV depth increased with distance from the optic disc (p=0.011) and CV size increased with distance from the fovea (p=0.005). There were no statistically significant associations between CVs and NPA, or between CVs and VA. CONCLUSIONS: WF SS OCTA revealed that a large fraction of CVs that form after BRVO are extramacular, and the morphology of CVs varies as a function of retinal location. Depth-resolved study of CVs may offer valuable insights on the pathophysiological mechanisms leading to the development of macular oedema.

Quantitative Wide-Field Swept-Source Optical Coherence Tomography Angiography and Visual Outcomes in RAO.

Purpose: Retinal artery occlusion (RAO) is an ophthalmic emergency that can lead to poor visual outcomes and is associated with an increased risk of stroke and cardiovascular events. Wide-field swept-source OCT-A (WF SS-OCTA) can provide quick and non-invasive angiographic information with a wide field of view. Here, we looked for associations between OCT-A vascular imaging metrics and vision in RAO patients. Methods: Patients with diagnoses of central (CRAO) or branched retinal artery occlusion (BRAO) were included. 6mm × 6mm Angio and 15mm × 15mm AngioPlex Montage OCT-A images were obtained for both eyes in each patient using Zeiss Plex Elite 9000 WF SS-OCTA device. Each 6mm × 6mm image was divided into nine Early Treatment Diabetic Retinopathy Study (ETDRS) subfields. Non-perfusion area (NPA) was manually measured using 15mm × 15mm images. A linear regression model was utilized to identify correlation between imaging metrics and vision. P-values less than 0.05 were considered as statistically significant. Results: Twenty-five subjects were included. For RAO eyes, there was a statistically significant inverse correlation between retinal thickness as well as superficial capillary plexus (SCP) vessel density (VD) and vision. An inverse correlation was found between deep capillary plexus (DCP) VD and vision without statistical significance. There was a positive correlation between choroidal thickness as well as choroidal volume and vision without statistical significance. No significant correlation was found between the metrics and vision in contralateral eyes. For NPA and vision, no significant correlation was identified. Conclusion: This is the first study to investigate the utility of WF SS-OCTA in RAO and to demonstrate correlations between retinal vascular imaging metrics and visual outcomes. The results of this study provide a basis to understand the structural changes involved in vision in RAO and may guide management of RAO and prevention of cerebral stroke and cardiovascular accidents.

Remodeling of H3K9me3 during the pluripotent to totipotent-like state transition.

Multiple chromatin modifiers associated with H3K9me3 play important roles in the transition from embryonic stem cells to 2-cell (2C)-like cells. However, it remains elusive how H3K9me3 is remodeled and its association with totipotency. Here, we integrated transcriptome and H3K9me3 profiles to conduct a detailed comparison of 2C embryos and 2C-like cells. Globally, H3K9me3 is highly preserved and H3K9me3 dynamics within the gene locus is not associated with gene expression change during 2C-like transition. Promoter-deposited H3K9me3 plays non-repressive roles in the activation of genes during 2C-like transition. In contrast, transposable elements, residing in the nearby regions of up-regulated genes, undergo extensive elimination of H3K9me3 and are tended to be induced in 2C-like transitions. Furthermore, a large fraction of trophoblast stem cell-specific enhancers undergo loss of H3K9me3 exclusively in MERVL+/Zscan4+ cells. Our study therefore reveals the unique H3K9me3 profiles of 2C-like cells, facilitating the further exploration of totipotency.

Wide-field swept-source optical coherence tomography angiography in the assessment of retinal microvasculature and choroidal thickness in patients with myopia.

BACKGROUND/AIMS: Pathological myopia (PM) is a leading cause of blindness worldwide. We aimed to evaluate microvascular and chorioretinal changes in different stages of myopia with wide-field (WF) swept-source (SS) optical coherence tomography angiography (OCTA). METHODS: This prospective cross-sectional observational study included 186 eyes of 122 patients who had undergone imaging between November 2018 and October 2020. Vessel density (VD) and vessel skeletonised density (VSD) of superficial capillary plexus, deep capillary plexus and whole retina, as well as foveal avascular zone parameters, retinal thickness (RT) and choroidal thickness (CT), were calculated. RESULTS: This study evaluated 75 eyes of 48 patients with high myopia (HM), 43 eyes of 31 patients with mild to moderate myopia and 68 eyes of 53 age-matched controls. Controlling for age and the presence of systemic hypertension, we found that HM was associated with decrease in VD and VSD in all layers on 12×12 mm² scans. Furthermore, HM was associated with a VD and VSD decrease in every Early Treatment Diabetic Retinopathy Study grid, with a larger decrease temporally (ßVD=-0.39, ßVSD=-10.25, p<0.01). HM was associated with decreased RT and CT. Reduction in RT was outside the macular region, while reduction in CT was in the macular region. CONCLUSION: Using WF SS-OCTA, we identified reduction in microvasculature and structural changes associated with myopia. Decrease in VD and VSD was greater in the temporal quadrant, and reductions in RT and CT were uneven across the retina. Further work may help identify risk factors for the progression of PM and associated vision-threatening complications.

Achieving Inner Aqueous Drain in Glaucoma Secondary to Iridocorneal Endothelial Syndrome: One Year Results of Penetrating Canaloplasty.

PURPOSES: To report the efficacy of a bleb-independent penetrating canaloplasty in the management of glaucoma secondary to iridocorneal endothelial syndrome (GS-ICE). DESIGN: Prospective, non-comparative clinical study. METHODS: Penetrating canaloplasty was performed on 35 eyes from 35 patients with GS-ICE and medically uncontrolled intraocular pressure (IOP) between January 2018 and April 2020. Patients were followed up at 1 week, months 1, 3, 6, 12 postoperatively, and semi-annually thereafter. The IOP, anti-glaucoma medication, and surgery-related complications were recorded. Surgical success was defined as IOP ≥ 5 mmHg and ≤ 21 mmHg without (complete success) or with/without (qualified success) IOP-lowering medication. RESULTS: A total of 29 eyes (82.9%) had 360° catheterization and successfully received penetrating canaloplasty. Of these eyes, 24 (82.8%) achieved qualified success and 22 (75.9%) achieved qualified success at 12 months after surgery. The mean IOP decreased from 39.5 ± 11.8 mmHg on 2.9 ± 1.0 medications before surgery to 16.6 ± 5.3 mmHg (P < .001) on 0.2 ± 0.6 medications (P < .001) at 12 months postoperatively, respectively. Hyphema (37.9%), transient hypotony (34.5%), and transient postoperative IOP elevation (≥ 30 mmHg, 17.9%) were the most commonly observed early complications at the 1 week and 1 month visits. From 1 month and beyond, all treated eyes showed no obvious bleb at the operation quadrant. CONCLUSIONS: Penetrating canaloplasty rescued the inner aqueous outflow in ICE eyes and demonstrated acceptable success in IOP control with few complications, providing a new option for the management of GS-ICE.

Efficacy of bleb-independent penetrating canaloplasty in primary angle-closure glaucoma: one-year results.

PURPOSE: To report the efficacy and safety of bleb-independent penetrating canaloplasty in the management of primary angle-closure glaucoma (PACG). METHODS: This single-centre prospective interventional case series enrolled 57 eyes from 53 PACG patients with medically uncontrolled intraocular pressure (IOP) and peripheral anterior synechiae of over 270°. Penetrating canaloplasty, mainly consisted of tensioning suture-aided Schlemm's canal dilation and a trabeculectomy, was performed to create a direct communication between the anterior chamber and the Schlemm's canal. Postoperative IOP, number of glaucoma medications and procedure-related complications were evaluated. Rate of success was defined as IOP ≤ 21, ≤18 and ≤15 mmHg, and a ≥30% IOP reduction without (complete) or with/without (qualified) IOP-lowering medications. RESULTS: A total of 45 eyes had 360° catheterization successfully completed. The mean preoperative IOP was 33.9 ± 11.7 mmHg (range, 13-59.6 mmHg), on 3.2 ± 0.8 glaucoma medications (range 2-5), which was decreased to 15.4 ± 3.7 mmHg (range, 8.6-22.5) and 0.2 ± 0.6 (range, 0-3) medications at 6 months and 14.8 ± 3.5 mmHg (range, 9-24) and 0.1 ± 0.3 (range, 0-1) medications at 12 months postoperatively. Complete success at 12 months were achieved in 78.9% (95% CI: 0.65-0.93), 71.1% (0.56-0.86) and 50.0% (0.33-0.67) eyes at IOP ≤ 21, ≤18 and ≤15 mmHg, respectively. Transient IOP elevation (>30 mmHg, 26.7%) and hyphema (11.1%) were the most common early surgical complications. CONCLUSION: Penetrating canaloplasty in PACG appeared to have good efficacy and safety profiles in this pilot study. Further studies are justified.