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Objective of Surgery: The aim of this surgical technique is the implantation of a glaucoma drainage device (GDD) in eyes with aphakic glaucoma following injector-assisted implantation of an artificial iris into the ciliary sulcus., Indications: This atraumatic tube insertion technique can be performed during GDD implantation after implantation of an artificial iris into the ciliary sulcus., Surgical Technique: Following injector-assisted implantation of an artificial iris into the ciliary sulcus of eyes, the iris can shift into the chamber angle. The GDD should be positioned in the quadrant in which the iridectomy is located. Otherwise, GDD implantation is not possible due to the resistance of the artificial iris. Alternatively, the artificial iris can be easily and non-traumatically rotated in the ciliary sulcus by flushing the anterior chamber with balanced salt solution (BSS) to move the iridectomy into the desired area and position the GDD tube in the anterior chamber. A surgical video, which is available online, shows the surgical technique in detail., Follow-Up: After GDD, dexamethasone eye drops should be applied 8 times daily for 1 week tapering down by 1 drop per week thereafter. Antibiotic eye drops, e.g., ofloxacin eye drops, are prescribed 4 times daily for 1 week and might be discontinued thereafter., Evidence: To date, this is the first description of a rotation of an artificial iris located in the ciliary sulcus by irrigation of the anterior chamber during GDD implantation., (© 2024. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Purpose: To compare the efficacy, safety, and factors influencing the outcomes of trabeculectomy (TE), conventional canaloplasty (cCP), and mitomycin C augmented canaloplasty (mCP) in glaucoma patients., Methods: Intraocular pressure (IOP), the number of IOP-lowering eye drops, and surgery-related complications were evaluated at baseline and through 18 months postoperatively. Correlations between patients' demographic data, ophthalmic and non-ophthalmic conditions, outcomes and complications were evaluated., Results: 171 patients were included. IOP and IOP-lowering eye drops were significantly (p < 0.001) reduced 18 months after TE, cCP, and mCP. At the 18-month follow-up, IOP and IOP-lowering eye drops were significantly lower following TE than cCP (p < 0.001, p = 0.010, respectively) and mCP (p = 0.010, p = 0.014). At the 18-month follow-up, complete success rates were significantly higher after TE compared to cCP and mCP for IOP ≤ 21, 18, and 16 mmHg (p < 0.001). Qualified success rates for IOP ≤ 16 mmHg were higher following TE than cCP and mCP (p = 0.023). In the TE group, clinical hypotony at any postoperative follow-up was positively correlated with previous intravitreal anti-vascular endothelial growth factor (VEGF)-therapy (p < 0.001), leukaemia (p = 0.002), and a spherical equivalent < -3 dioptres (p < 0.001). There were no significant correlations in the cCP and mCP groups., Conclusion: TE, cCP, and mCP led to a significant reduction in IOP and IOP-lowering eye drops during 18 months of follow-up. At 18 months of follow-up, IOP and IOP-lowering eye drops were significantly lower following TE compared to cCP and mCP. Anti-VEGF-therapy, cystostatic therapy in leukaemia, and a spherical equivalent < -3 dioptres were significantly correlated with postoperative hypotony, macular folds, and choroidal detachment in the TE group., Key Messages: What is known • Trabeculectomy (TE) is considered the gold standard in the surgical management of glaucoma. However, TE involves extensive postoperative management and might be associated with severe surgery-related complications. What is new • In this study, intraocular pressure (IOP) and IOP-lowering eye drops were significantly lower following TE compared to conventional canaloplasty (cCP) and mitomycin C augmented canaloplasty (mCP) at a follow-up of 18 months. • In patients undergoing TE, anti-VEGF-therapy, cystostatic therapy in leukaemia, and a spherical equivalent < -3 dioptres were significantly correlated with postoperative hypotony, macular folds, and choroidal detachment., (© 2024. The Author(s).)

The retina is part of the central nervous system (CNS). Neurons in the CNS and retinal ganglion cells lack the ability to regenerate axons spontaneously after injury. The intrinsic axonal growth regulators, their interaction and roles that enable or inhibit axon growth are still largely unknown. This study endeavored to characterize the molecular characteristics under neurodegenerative and regenerative conditions. Data-Independent Acquisition Mass Spectrometry was used to map the comprehensive proteome of the regenerative retina from 14-day-old mice (Reg-P14) and adult mice after lens injury (Reg-LI) both showing regrowing axons in vitro, untreated adult mice, and retina from adult mice subjected to two weeks of elevated intraocular pressure showing degeneration. A total of 5750 proteins were identified (false discovery rate < 1%). Proteins identified in both Reg-P14 and Reg-LI groups were correlated to thyroid hormone, Notch, Wnt, and VEGF signaling pathways. Common interactors comprising E1A binding protein P300 (EP300), CREB binding protein (CBP), calcium/calmodulin dependent protein kinase II alpha (CaMKIIα) and sirtuin 1 (SIRT1) were found in both Reg-P14 and Reg-LI retinas. Proteins identified in both regenerating and degenerative groups were correlated to thyroid hormone, Notch, mRNA surveillance and measles signaling pathways, along with PD-L1 expression and the PD-1 checkpoint pathway. Common interactors across regenerative and degenerative retinas comprising NF-kappa-B p65 subunit (RELA), RNA-binding protein with serine-rich domain 1 (RNPS1), EP300 and SIN3 transcription regulator family member A (SIN3A). The findings from our study provide the first mapping of regenerative mechanisms across postnatal, mature and degenerative mouse retinas, revealing potential biomarkers that could facilitate neuro-regeneration in glaucoma., (© 2024. The Author(s).)

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., (© 2024. The Author(s).)

Background/aims: The goal of health research is to improve patients care and outcomes. Thus, it is essential that research addresses questions that are important to patients and clinicians. The aim of this study was to develop a list of priorities for glaucoma research involving stakeholders from different countries in Europe., Methods: We used a three-phase method, including a two-round electronic Delphi survey and a workshop. The clinician and patient electronic surveys were conducted in parallel and independently. For phase I, the survey was distributed to patients from 27 European countries in 6 different languages, and to European Glaucoma Society members, ophthalmologists with expertise in glaucoma care, asking to name up to five research priorities. During phase II, participants were asked to rank the questions identified in phase I using a Likert scale. Phase III was a 1 day workshop with patients and clinicians. The purpose was to make decisions about the 10 most important research priorities using the top 20 priorities identified by patients and clinicians., Results: In phase I, 308 patients and 150 clinicians were involved. In phase II, the highest-ranking priority for both patients and clinicians was 'treatments to restore vision'. In phase III, eight patients and four clinicians were involved. The top three priorities were 'treatments to stop sight loss', 'treatments to restore vision' and 'improved detection of worsening glaucoma'., Conclusion: We have developed a list of priorities for glaucoma research involving clinicians and patients from different European countries that will help guide research efforts and investment., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

Purpose: To evaluate the mid-term clinical results and the safety aspects of the Hydrus ® Microstent (Ivantis, Inc, Irvine, CA) in a real-life setting., Design: Retrospective case series., Methods: Hydrus ® Microstent was implanted in phakic eyes (88 eyes, 87.1%) and in pseudophakic eyes (13 eyes, 12.9%), respectively. Mean follow-up time was 16 ± 9 months with 27 eyes having a follow-up time of more than 24 months., Main Outcome Measures: The primary endpoint was reduction in IOP compared to baseline. Target IOP levels were set at ≤20 mmHg, ≤18 mmHg and ≤15 mmHg. Kaplan-Meier survival was defined as a reduction in IOP of ≥20% compared to baseline. Secondary endpoints were reduction in number of glaucoma medications and safety assessments addressing visual acuity, adverse events, re-surgery rate and identification of factors that made the implantation more difficult., Result: 101 eyes underwent Hydrus ® implantation. The mean preoperative IOP was 21.60 mmHg (SD 6.6) on 2.18 (SD 1.3) medications. After a mean follow up time of 16 months, the mean IOP was reduced to 14.61 ± 3.7 mmHg on 1.12 (SD 1.1) medication classes (p < 0.001). Mean decrease in IOP was 26.7%. Analysis of the target IOP levels showed that in 29%, 34% and 35% of cases an IOP of ≤15 mmHg, ≤18 mmHg and ≤20 mmHg respectively could be achieved. BCVA improved from 0.56 ± 0.3 at baseline to 0.85 ± 0.3 more than 24 months after surgery (p < 0.001). The rate of re-operation was low at <3%. Adverse events occurred in 4 eyes (<4%)., Conclusion: This study underlines the effectiveness and the safety of the Hydrus ® Microstent in an elective setting, but it also demonstrates certain limits and risk factors of this procedure., (© 2024. The Author(s), under exclusive licence to The Royal College of Ophthalmologists.)

Purpose: To investigate whether trabecular aspiration (TA) has an effective medium-term intraocular pressure (IOP)-lowering and medication-saving effect in patients with pseudoexfoliation glaucoma (PEG). In addition, a subgroup analysis of patients with or without a previous trabeculectomy was performed., Methods: Records of 290 consecutive eyes with PEG that underwent TA between 2006 and 2012 at the Department of Ophthalmology, Mainz, Germany, were retrospectively analyzed with a follow-up period of 3 years. The main outcomes were IOP and the need for further medical treatment., Results: Of the 290 eyes with PEG that received TA, 167 eyes from 127 patients met the inclusion criteria. Among these eyes, 128 received TA and cataract surgery (Phaco-TA) without having had a trabeculectomy (group I) before, 29 had Phaco-TA after a previous trabeculectomy (group II) and 10 underwent stand-alone TA after a previous trabeculectomy (group III). In the whole cohort, the median IOP decreased immediately after TA and remained significantly lower compared to the baseline throughout the period of 36 months. Likewise, the median number of antiglaucoma drugs was reduced over the whole period. At the same time, in group I, the median IOP and the number of antiglaucoma drugs were reduced over 36 months. In contrast, in the post-trabeculectomy groups (group II and III), the median IOP and the number of antiglaucoma drugs could not be reduced. While most of the patients that received Phaco-TA with or without a previous trabeculectomy (group I and II) did not require further surgical intervention during the follow-up period, almost all patients receiving stand-alone TA after a previous trabeculectomy (group III) needed surgical therapy, most of them between the second and the third year following TA., Conclusions: Phaco-TA has an effective medium-term pressure-lowering and medication-saving effect, especially in patients without a previous trabeculectomy. In trabeculectomized eyes, the effect of TA is limited but still large enough to delay more invasive surgical interventions in some patients.

Background: NADPH oxidase (NOX), a primary source of endothelial reactive oxygen species (ROS), is considered a key event in disrupting the integrity of the blood-retinal barrier. Abnormalities in neurovascular-coupled immune signaling herald the loss of ganglion cells in glaucoma. Persistent microglia-driven inflammation and cellular innate immune system dysregulation often lead to deteriorating retinal degeneration. However, the crosstalk between NOX and the retinal immune environment remains unresolved. Here, we investigate the interaction between oxidative stress and neuroinflammation in glaucoma by genetic defects of NOX2 or its regulation via gp91ds-tat., Methods: Ex vivo cultures of retinal explants from wildtype C57BL/6J and Nox2 -/- mice were subjected to normal and high hydrostatic pressure (Pressure 60 mmHg) for 24 h. In vivo, high intraocular pressure (H-IOP) was induced in C57BL/6J mice for two weeks. Both Pressure 60 mmHg retinas and H-IOP mice were treated with either gp91ds-tat (a NOX2-specific inhibitor). Proteomic analysis was performed on control, H-IOP, and treatment with gp91ds-tat retinas to identify differentially expressed proteins (DEPs). The study also evaluated various glaucoma phenotypes, including IOP, retinal ganglion cell (RGC) functionality, and optic nerve (ON) degeneration. The superoxide (O 2 - ) levels assay, blood-retinal barrier degradation, gliosis, neuroinflammation, enzyme-linked immunosorbent assay (ELISA), western blotting, and quantitative PCR were performed in this study., Results: We found that NOX2-specific deletion or activity inhibition effectively attenuated retinal oxidative stress, immune dysregulation, the internal blood-retinal barrier (iBRB) injury, neurovascular unit (NVU) dysfunction, RGC loss, and ON axonal degeneration following H-IOP. Mechanistically, we unveiled for the first time that NOX2-dependent ROS-driven pro-inflammatory signaling, where NOX2/ROS induces endothelium-derived endothelin-1 (ET-1) overexpression, which activates the ERK1/2 signaling pathway and mediates the shift of microglia activation to a pro-inflammatory M1 phenotype, thereby triggering a neuroinflammatory outburst., Conclusions: Collectively, we demonstrate for the first time that NOX2 deletion or gp91ds-tat inhibition attenuates iBRB injury and NVU dysfunction to rescue glaucomatous RGC loss and ON axon degeneration, which is associated with inhibition of the ET-1/ERK1/2-transduced shift of microglial cell activation toward a pro-inflammatory M1 phenotype, highlighting NOX2 as a potential target for novel neuroprotective therapies in glaucoma management., (© 2024. The Author(s).)