Effects of elevated intraocular pressure on alpha ganglion cells in experimental glaucoma mice.

Glaucoma is a leading cause of blindness worldwide and glaucoma patients exhibit an early diffuse loss of retinal sensitivity followed by focal loss of RGCs. Combining some previous published results and some new data, this paper provides our current view on how high IOP (H-IOP) affects the light response sensitivity of a subset of RGCs, the alpha-ganglion cells (αGCs), as well as their presynaptic bipolar cells (DBCs and HBCs) and A2 amacrine cells (AIIACs) in dark-adapted mouse retinas. Our data demonstrate that H-IOP in experimental glaucoma mice significantly decreases light-evoked spike response sensitivity of sONαGCs and sOFFαGCs (i.e., raises thresholds by 1.5-2.5 log units), but not that of the tONαGCs and tOFFαGCs. The sensitivity loss in sONαGCs and sOFFαGCs is mediated by a H-IOP induced suppression of AIIAC response which is caused by a decrease of transmission efficacy of the DBCR→AIIAC synapse. We also provide evidence supporting the hypothesis that BK channels in the A17AC→DBCR feedback synapse are the H-IOP sensor that regulates the DBCR→AIIAC synaptic efficacy, as BK channel blocker IBTX mimics the action of H-IOP. Our results provide useful information for designing strategies for early detection and possible treatments of glaucoma as physiological changes occur before irreversible structural damage.

Evaluation of agreement of IOP measurements by Tono-Vera tonometer to Goldmann applanation tonometry.

Purpose: To evaluate the accuracy of the new Tono-Vera rebound tonometer (Reichert Inc, Buffalo, NY) compared to Goldmann Applanation Tonometry. Methods: This prospective, observational, cross-sectional study was designed in accordance with ANSI Z80.10-2014 and ISO 8612-2009 guidelines for tonometer comparison. Intraocular Pressure (IOP) was measured by Goldmann Applanation and Tono-Vera on 160 eyes of 160 subjects. Corneal Astigmatism and Central Corneal Thickness were also measured. A single investigator (CN) conducted all measurements. The average of two measurements from each tonometer was used in the analysis. Bland-Altman plots, total least squares regression analysis, and simple linear regression were used to evaluate agreement between the tonometers. Results: Average IOP values from Goldmann Applanation and Tono-Vera were not significantly different (19.17 and 19.03 respectively, p=0.40, paired t-test). The total least squares regression analysis indicated strong agreement between the two tonometers (slope +0.97, offset +0.49 mmHg, standard deviation 2.11 mmHg). There were 2 IOP measurement pairs that exceeded the ± 5 mmHg limits of agreement required in ANSI Z80.10-2014 and ISO 8612-2009, which is within the range of acceptability specified in the standards. Conclusion: We evaluated IOP measurements by Tono-Vera Rebound Tonometer vs Goldmann Applanation Tonometry for eyes with a wide range of IOP values and found no statistically significant differences in the results. Tono-Vera meets the requirements of ANSI Z80.10-2014 and ISO 8612-2009, demonstrating accuracy comparable to Goldmann tonometry.

Clinical observations of EVO-ICL implantation with single incision without viscoelastic agent.

BACKGROUND: To investigate the safety and effectiveness of non-viscoelastic agent technique for EVO-ICL implantation. METHODS: A total of 181 myopia eyes that underwent non-toric ICL without viscoelastic agent through single incision from Beijing Tongren Hosipital were included. An analysis was conducted on the quantity of haptics that were initially implanted intraoperatively into the posterior chamber. Intraocular pressure (IOP) was evaluated at before and 2 h,24 h,1week,6month after surgery. Anterior chamber volume(ACV), anterior chamber depth(ACD), anterior chamber angle(ACA), pupil diameter(PD) and corneal densitometry density (ECD) were evaluated at before and 24 h postoperatively. Refractive outcomes were investigated at before, 24 h ,7 days and 6months. Vault was evaluated at 24 h ,7 days and 6months. RESULTS: The efficacy and safety indices were 1.30 ± 0.32 and 1.31 ± 0.32, respectively. Of 181 eyes, 99 eyes received 4 haptics on the first attempt without any adjustment, and 72 eyes received lens alignment without an viscoelastic agent. The success rate of the viscoelastic agent free procedure was 94.5%. Two hours postoperatively, IOP was 17.41 ± 3.77 mmHg, which was significantly higher than baseline value (t = 8.930, P < 0.000), however there was no significant difference between preoperative IOP and IOP at 1 day ,1 week and 6 months postoperatively. The ECD changed from 2895.52 ± 253.73 cells/mm2 preoperatively to 2873.66 ± 244.17 cells/mm2 at 1 day and 2882.63 ± 239.97 postoperatively, and the difference was not statistically significant (t = 1.811, P = 0.072). The ACA was narrowed by 42% on the first day. CONCLUSION: The pure viscoelastic agent free technique is an efficient and safe way for ICL implantation. It can be a safer method of ICL implantation because of it reduces the risk of complications associated with ocular hypertension at the early postoperative stages. TRIAL REGISTRATION: Chinese Clinical Trial Registry (ChiCTR2000036335) at August 20, 2020.

Clinical Outcomes of Excisional Goniotomy with the Kahook Dual Blade: 6-Year Results.

INTRODUCTION: This study aims to evaluate the long-term clinical outcomes of excisional goniotomy with the Kahook Dual Blade (KDB) in the management of various types of glaucoma. METHODS: This was a retrospective, noncomparative chart review of 90 eyes of 53 patients with glaucoma that underwent standalone KDB goniotomy (KDB-alone group) or KDB goniotomy with concomitant phacoemulsification (KDB-phaco group) between October 2015 and October 2017. Surgical success was defined as an intraocular pressure (IOP) reduction by ≥ 20% at the last follow-up with no surgical reinterventions required and a final IOP ≥ 4 mmHg and ≤ 21 mmHg. We also report on changes from baseline in IOP, number of glaucoma medications, best-corrected visual acuity (BCVA), and visual field parameters, for up to 72 months. RESULTS: At 72 months, mean (standard deviation [SD]) IOP was reduced from 17.5 (5.7) to 13.6 (3.0) mmHg (P < 0.0001) in the KDB-phaco group and from 23.3 (5.9) to 15.1 (6.2) mmHg (P = 0.0593) in the KDB-alone group. The mean (SD) number of glaucoma medications was reduced from 1.3 (1.0) to 0.8 (0.9) (P < 0.0001) in the KDB-phaco group and from 1.2 (1.0) to 0.7 (0.8) (P = 0.3409) in the KDB-alone group. During the 72-month follow-up, surgical success was achieved in 24 of the 52 available eyes (46.2%). Four eyes underwent a glaucoma surgical reintervention by 72 months. CONCLUSIONS: Excisional goniotomy with the KDB effectively lowered the IOP (by an average of 28.0% from baseline) and maintained or further reduced glaucoma medication burdens (by an average of 30.8% from baseline) under an excellent safety profile, independent of phacoemulsification status. The procedure exhibited favorable success for up to 6 years, providing valuable insights into its long-term efficacy as a glaucoma treatment.

A Comprehensive Review of Recent Advances in Minimally Invasive Glaucoma Surgery: Current Trends and Future Directions.

Glaucoma, a leading cause of blindness globally, necessitates effective management strategies to prevent irreversible vision loss. Traditional glaucoma surgeries, while effective, are associated with significant risks and complications. Minimally invasive glaucoma surgery (MIGS) has emerged as a transformative approach, offering safer and less invasive alternatives. This review provides a comprehensive overview of recent advancements in MIGS, highlighting current trends, technological innovations, and future directions. MIGS procedures, characterized by smaller incisions and quicker recovery times, have expanded the therapeutic landscape, enabling earlier intervention and improved patient outcomes. The review evaluates various MIGS techniques, their efficacy, safety profiles, and clinical outcomes, drawing insights from comparative studies and meta-analyses. Technological innovations, including enhanced device designs and integration with digital health technologies, have further bolstered the field. Despite challenges in patient selection and long-term outcomes, the future of MIGS is promising, with ongoing research and development poised to enhance its impact. By synthesizing the latest research, this review aims to inform clinicians, researchers, and policymakers, ultimately contributing to improved management of glaucoma and patient care.

Mechanosensitive ion channels in glaucoma pathophysiology.

Force sensing is a fundamental ability that allows cells and organisms to interact with their physical environment. The eye is constantly subjected to mechanical forces such as blinking and eye movements. Furthermore, elevated intraocular pressure (IOP) can cause mechanical strain at the optic nerve head, resulting in retinal ganglion cell death (RGC) in glaucoma. How mechanical stimuli are sensed and affect cellular physiology in the eye is unclear. Recent studies have shown that mechanosensitive ion channels are expressed in many ocular tissues relevant to glaucoma and may influence IOP regulation and RGC survival. Furthermore, variants in mechanosensitive ion channel genes may be associated with risk for primary open angle glaucoma. These findings suggest that mechanosensitive channels may be important mechanosensors mediating cellular responses to pressure signals in the eye. In this review, we focus on mechanosensitive ion channels from three major channel families-PIEZO, two-pore potassium and transient receptor potential channels. We review the key properties of these channels, their effects on cell function and physiology, and discuss their possible roles in glaucoma pathophysiology.

Phacoemulsification combined with Kahook Dual Blade Goniotomy versus with Trabectome in the treatment of open angle glaucoma.

PURPOSE: To compare the surgical effectiveness and safety of phacoemulsification combined with KDB (Phaco-KDB) and with Trabectome (Phaco-Trabectome) at 6 months follow-up in patients with open-angle glaucoma (OAG) METHODS: This comparative case series was conducted at Beijing Tongren Hospital, including patients diagnosed with OAG who underwent Phaco-KDB from November 2021 to April 2022 and Phaco-Trabectome from April 2017 to December 2017. Surgical success was defined as an IOP reduction ≥ 20% or a postoperative IOP ≤ 21 mmHg. Kaplan-Meier methods were used to calculate cumulative rates of success among groups RESULTS: A total of 35 eyes from 29 patients were included in the analysis. At 6-month, Both groups exhibited a significant reduction in IOP and the number of IOP-lowering medications compared to preoperative (P=0.01 and P<0.01, respectively). There were no significant differences among groups in terms of reducing IOP and the number of IOP-lowering medications (all P values<0.05). In the Phaco-KDB and Phaco-Trabectome groups, 53.8% and 45.0% of patients achieved an IOP reduction of ≥ 20%, while 92.3% and 85% achieved a mean IOP ≤ 21 mmHg 6 months after surgery. The incidence of IOP spike was 20%, and 3 eyes (8.6%) needed further surgery to control the IOP CONCLUSIONS: Both Phaco-KDB and Phaco-Trabectome demonstrate a significant reduction in IOP and the number of IOP-lowering medications. Phaco-Trabectome appears to provide a more predictable postoperative course in the early postoperative period compared to Phaco-KDB, and the postoperative mean IOP is lower in Phaco-KDB compared to Phaco-Trabectome, despite not being statistically significant.

The positive impact of identity-affirming mental health treatment for neurodivergent individuals.

Introduction: The medical and social definitions of neurodivergence have become a common topic of discussion in recent years, and the ways that we define, measure and report on conditions within the neurodivergent umbrella are changing. The objective of this study was to analyze differences in mental health symptom presentation at intake and compare treatment outcomes among three groups: clients with an affirming neurodivergent diagnosis, clients without an affirming diagnosis, and neurotypical clients. Methods: Data were collected at intake and discharge. Clients self-reported neurodivergent identity, neurodivergent diagnoses, as well as the severity of depression symptoms, anxiety symptoms and self-harm frequency. One-way multivariate analysis of variance tests were run to assess differences in mental health symptoms at intake and discharge based on neurodivergent identity and corresponding diagnosis. When MANOVAs indicated significant differences, follow-up univariate one-way ANOVAs were conducted for each dependent variable. Results: Neurodivergent clients reported significantly worse mental health symptoms at intake than neurotypical clients, regardless of diagnosis status. Additionally, clients who identified as neurodivergent but did not report an affirming medical diagnosis reported significantly worse mental health symptoms than those who did report an affirming medical diagnosis. By discharge from IOP treatment, no significant differences were found in symptom change scores between neurodivergent and neurotypical individuals, or neurodivergent individuals with an affirming diagnosis and those without. Discussion: These findings highlight the importance of acknowledging client identity as a key component of mental health treatment. The act of validating symptoms and experiences, allowing accommodations when requested, and exploring identity formation regardless of diagnosis, allowed all clients who identified as neurodivergent to benefit from treatment.

Assessing the Impact of PRESERFLO MicroShunt on Intraocular Pressure in Porcine Eyes Ex Vivo Using Infusion Pump System.

To evaluate the effectiveness of the PRESERFLO MicroShunt (PFM) in reducing intraocular pressure (IOP) ex vivo in porcine eyes using an infusion pump system and to simulate various IOP conditions, In this study, porcine eyes received increasing flows between 2 and 20 µL/min. IOP measurements were taken under conditions with and without the PFM [PFM (+) and PFM (-), respectively]. In the PFM (-) group, IOP increased from 7.4 mmHg to 46.3 mmHg as the flow rate increased from 2 µL/min to 20 µL/min. The rate of IOP reduction (%ΔIOP) rose with increasing flow rates, although the absolute IOP values achieved with the PFM insertion also increased. The correlation between IOPs in the PFM (-) conditions and the %ΔIOP was modeled as %ΔIOP = 22.4 Ln [PFM(-) IOP] - 41.7. According to this equation, IOP reduction by PFM insertion is 0% at IOPs of 6.4 mmHg or lower. IOP reductions of 10%, 20%, 30%, and 40% were observed when the pre-insertion IOPs were 10.1, 15.7, 24.6, and 38.4 mmHg, respectively. Achievable post-insertion IOP levels of ≤21 mmHg, ≤18 mmHg, ≤15 mmHg, and ≤12 mmHg corresponded to the initial IOPs of 33 mmHg, 26 mmHg, 20 mmHg, and 14.8 mmHg, respectively. In conclusion, the PFM effectively reduced IOP within a specific range of IOP values in an ex vivo experimental system. In clinical situations, the PFM is unlikely to be effective at low IOP levels. At higher levels, the PFM reduces IOP, but it may be insufficient to achieve the target IOP.

The Achievement of IOP Target Among a Sample of Iraqi Patients with Glaucoma: A Retrospective Study.

Background: Glaucoma is a chronic progressive eye disorder. It is the primary cause of blindness. To prevent glaucomatous damage and blindness, the intra-ocular pressure (IOP) must be lowered to certain levels, this level is known as "IOP" target. Many studies conducted in developed countries have found that the majority of glaucoma patients failed to reach their target IOP. Purpose: This study aimed to assess the achievement of IOP target among Iraqi patients with glaucoma and to determine the factors affecting it. Patients and Methods: A single-center retrospective cohort study was conducted by inspecting the records of all patients with confirmed cases of glaucoma who were admitted to the Ibn-Al-Haitham Hospital outpatient unit from January 2020 to December 2022. To be included in the study, the patient must be newly diagnosed with glaucoma. In addition, full information on the patient's demographics, medical therapy used, and IOP at baseline and after 1 month of treatment must be available in the patient's case sheet. After considering the study inclusion criteria, the records of 760 patients were excluded, and only 100 patients were eligible. Results: The included patients were mostly males, with an average age of 57.86 years. A 70% of the patients had elevated IOP in both eyes. Most patients (38%) were treated with two anti-glaucoma drugs. Only 35% of the patients achieved their targeted IOP. Regarding the factors influencing the achievement of the IOP target, all demographic data (age and gender) had a non-significant effect, while the number of prescribed drugs affected the ability of the patient to reach the IOP target. Conclusion: Most of Iraqi glaucomatous patients do not achieve their IOP target. The number of prescribed eye drops can significantly affect the ability of glaucoma patients to reach their targeted IOP.

A comparison of intraocular pressure measurement using SUOER SW-500 rebound tonometer and conventional reusable Goldmann prisms.

Introduction: To determine the agreement between intraocular pressure (IOP) measurements using conventional Goldmann applanation tonometry (GA1,2T) and SUOER SW-500 Rebound Tonometer. Methods: This was a retrospective observational study where 205 eyes of 106 glaucoma patients had their IOPs measured by 2 fellowship trained ophthalmologists. Data were analyzed using the Bland-Altman method of differences. Correlation was measured using the Pearson coefficient. Results: Most of our patients were Chinese (88.7%) and female (51.9%). The average age was 66.9 years. The range of IOPs as measured by GAT was 2 to 58 mm Hg. Using the Bland-Altman method to compare GAT and SUOER SW-500 Rebound Tonometer. The tonometer overestimated the IOP by 0.5 mm Hg in the right eye and underestimated it by 0.1 mm Hg in the left eye. Overall, the tonometer overestimated the IOP by 0.2 mmHg. The Tonometer IOP correlated well with GAT, with a Pearson coefficient of correlation(r) of 0.89 (p < 0.001) for the right eye and 0.86 (p < 0.001) for the left eye, respectively. In patients with GAT IOP ≥ 21 mm Hg (n = 25), the Tonometer underestimated the IOP by 2.96 mm Hg. Discussion: The IOP measurements from the SUOER SW-500 Rebound Tonometer correlates well with the conventional GAT in measuring the IOP within normal ranges of IOP. SUOER SW-500 Rebound Tonometer may be of use, especially if the risk of transmission of infection is high considering that the probes are disposable. It is easy to use and its small size and portability makes it useful in situations where the patient is unable to be examined at the slit lamp.

Changes of aqueous humor cytokine profiles of patients with high intraocular pressure after PPV for retinal detachment.

High intraocular pressure (IOP) is one of the early complications after pars plana vitrectomy (PPV), which may cause glaucoma and poor visual prognosis secondary to surgery. Proliferative vitreoretinopathy (PVR) is one of the complications of retinal detachment (RD) and is the main reason for the poor prognosis, which is related to different kinds of cytokines. It's essential for the basic mechanism to analyze the relative aqueous humor cytokine profiles with IOP after PPV for RD. In this study, we have collected the aqueous humor of 16 patients and qualified 27 cytokines using Luminex and compared biomarkers with the high IOP group and the normal group. As a result, the concentrations of VEGF, IL-6, FGF2, and G-CSF upregulated significantly (P < 0.05), while VEGFR2 downregulated significantly (P < 0.05) in the high IOP group. IL-6 was positively correlated with high IOP (r = 0.561, P = 0.041). Meanwhile, the concentrations of IL-6 (r = 0.543, P = 0.03), IL-5 (r = 0.576, P = 0.019), IL-15 (r = 0.614, P = 0.011), IL-4 (r = 0.517, P = 0.04), ICAM-1 (r = 0.611, P = 0.012), and G-CSF (r = 0.636, P = 0.008) were significantly associated with preoperative PVR classification, and the aqueous humor levels of IL-4 (r = 0.567, P = 0.022), HGF (r = 0.701, P = 0.005), and MCP-1 (r = 0.565, P = 0.035) are significant relative to laser points. Hence, cytokines might potentially be the therapeutic target of high IOP after PPV.

Sustained Release Therapies with the Prostaglandin Analogues Intracameral Implants.

The travoprost intracameral implant was recently approved by the US Food and Drug Administration for sustained release medical treatment of open-angle glaucoma in the USA. The approval represents a substantial and progressive step forward in the area of sustained-release glaucoma therapy. Topical intraocular pressure-lowering medications for the treatment of glaucoma are faced with a host of challenges for long-term and usually lifelong care. A changing paradigm in glaucoma management involves first-line interventions with laser modalities, micro-invasive surgeries, and sustained-release treatment platforms. Future needs in the area of sustained-release therapy include a non-prostaglandin drug delivery platform and longer-term treatments that do not require surgical reintervention.

A new self-adjustable glaucoma valve.

Introduction: Glaucoma, the leading cause of irreversible blindness globally, affects more than 70 million people across the world. When initial treatments prove ineffective, especially for cases with high intraocular pressure (IOP), the preferred approach involves employing glaucoma drainage devices (GDDs). Methods: This study introduces a novel self-adjustable glaucoma drainage device (SAGDD) designed to maintain IOP within the desired biological range (10 mmHg < IOP <18 mmHg) by dynamically modulating its fluidic resistance. Inspired by the starling resistor, we designed a circular valve with a thin, flexible membrane placed over the valve's inlet and outlet. To achieve the ideal design for the SAGDD and optimize its parameters, we utilized fluid-solid interaction (FSI) numerical models and conducted parametric studies, wherein simulations demonstrated the validity of the concept. Subsequently, to confirm and validate the numerical results, we fabricated a SAGDD at a 3:1 scale and subjected it to in vitro testing. Results: Our findings demonstrate that, on a 3:1 scale, a circular SAGDD with a diameter of 8.1 mm and a stainless-steel membrane with a thickness of 10 µm effectively maintained IOP within the target range when the membrane exposed to external pressures of 7.5 or 10 mmHg. Discussion: In summary, our study establishes a strong foundation for further exploration of the potential efficacy of SAGDD as a promising treatment for glaucoma. The cost-effectiveness and simplicity of its design, devoid of costly instrumentation, hold considerable promise in addressing the challenges associated with glaucoma.

[Effect of refractive surgery on Maklakov tonometry results]. / Vliyanie keratorefraktsionnoi khirurgii na rezul'taty tonometrii po Maklakovu.

PURPOSE: The study investigates the influence of changes in keratometric parameters after refractive surgery on the results of Maklakov tonometry. MATERIAL AND METHODS: The study examined a total of 61 people (121 eyes). The patients were divided into a control group with no history of surgery (16 people, 31 eyes), a LASIK group (13 people, 26 eyes), a femtosecond-assisted LASIK (FS-LASIK) group (16 people, 32 eyes), and a photorefractive keratectomy (PRK) group (16 people, 32 eyes). The patients underwent standard examination, keratometry (Km), Maklakov tonometry with a 10 g weight, and elastotonometry with 5, 7.5, and 15 g weights. RESULTS: In the LASIK group, the indentation diameter with 5 and 7.5 g weights correlated with Km in the central and near-paracentral zone (r=0.3-0.5). Tonometry with a 10 g weight did not correlate with anything. Tonometry with a 15 g weight inversely correlated with Km in the paracentral points (4 mm) of the strong meridian (r= -0.5 ... -0.7). In the FS-LASIK group, a significant inverse correlation with Km was observed only for the indentation diameter with a 10 g weight in the paracentral (3-4 mm) zone (r= -0.4 ... -0.5). In the PRK group, weak (r<0.4) correlations were found between Km and the indentation diameter of the 7.5 and 10 g weights for the central zone (1-2 mm). No significant correlations were found for 5 and 15 g weights.In the control group, there were practically no correlations for 5 and 7.5 g weights. The indentation diameter of the 10 g weight evenly correlated with Km at all points (r= -0.38 ... -0.60), the indentation of the 15 g weight correlated mainly with the curvature of the horizontal meridian (r= -0.37 ... -0.49). CONCLUSION: Tonometry readings with the 10 g weight are the most dependent on Km in different groups, and the readings with the 5 g weight are the least dependent. LASIK is characterized by the largest scatter of dependencies for weights of different masses, FS-LASIK - by the smallest. Tonometry readings with the 5 g weight correlated with Km only in the LASIK group, and this was the only direct correlation. Considering the inverse nature of most correlations, higher Km may be associated with an overestimation of tonometry results, and lower Km - with its underestimation.

A new mouse-fixation device for IOP measurement in awake mice.

Glaucoma is an irreversible blinding eye disease. The mechanisms underlying glaucoma are complex. Up to now, no successful remedy has been found to completely cure the condition. High intraocular pressure (IOP) is an established risk factor for glaucoma and the only known modifiable factor for glaucoma treatment. Mice have been widely used to study glaucoma pathogenesis. IOP measurement is an important tool for monitoring the potential development of glaucomatous phenotypes in glaucoma mouse models. Currently, there are two methods of IOP measurement in mice: invasive and non-invasive. As the invasive method can cause corneal damage and inflammation, and most of the noninvasive method involves the use of anesthetics. In the course of our research, we designed a mouse fixation device to facilitate non-invasive measurements of mouse IOPs. Using this device, mouse IOPs can be accurately measured in awake mice. This device will help researchers to accurately assess mouse IOP without the use of anesthetics.

Discussion paper: implications for the further development of the successfully in emergency medicine implemented AUD2IT-algorithm.

The AUD2IT-algorithm is a tool to structure the data, which is collected during an emergency treatment. The goal is on the one hand to structure the documentation of the data and on the other hand to give a standardised data structure for the report during handover of an emergency patient. AUD2IT-algorithm was developed to provide residents a documentation aid, which helps to structure the medical reports without getting lost in unimportant details or forgetting important information. The sequence of anamnesis, clinical examination, considering a differential diagnosis, technical diagnostics, interpretation and therapy is rather an academic classification than a description of the real workflow. In a real setting, most of these steps take place simultaneously. Therefore, the application of the AUD2IT-algorithm should also be carried out according to the real processes. A big advantage of the AUD2IT-algorithm is that it can be used as a structure for the entire treatment process and also is entirely usable as a handover protocol within this process to make sure, that the existing state of knowledge is ensured at each point of a team-timeout. PR-E-(AUD2IT)-algorithm makes it possible to document a treatment process that, in principle, does not have to be limited to the field of emergency medicine. Also, in the outpatient treatment the PR-E-(AUD2IT)-algorithm could be used and further developed. One example could be the preparation and allocation of needed resources at the general practitioner. The algorithm is a standardised tool that can be used by healthcare professionals of any level of training. It gives the user a sense of security in their daily work.

Iopanoic acid alters thyroid hormone-related gene expression, thyroid hormone levels, swim bladder inflation, and swimming performance in Japanese medaka.

Disruption of the thyroid hormone system by synthetic chemicals is gaining attention owing to its potential negative effects on organisms. In this study, the effects of the dio-inhibitor iopanoic acid (IOP) on the levels of thyroid hormone and related gene expression, swim bladder inflation, and swimming performance were investigated in Japanese medaka. Iopanoic acid exposure suppressed thyroid-stimulating hormone ß (tshß), tshß-like, iodotyronin deiodinase 1 (dio1), and dio2 expression, and increased T4 and T3 levels. In addition, IOP exposure inhibited swim bladder inflation, reducing swimming performance. Although adverse outcome pathways of thyroid hormone disruption have been developed using zebrafish, no adverse outcome pathways have been developed using Japanese medaka. This study confirmed that IOP inhibits dio expression (a molecular initiating event), affects T3 and T4 levels (a key event), and reduces swim bladder inflation (a key event) and swimming performance (an adverse outcome) in Japanese medaka.

An Evaluation of the Efficacy and Safety of Timolol Maleate 0.5% Microdrops Administered with the Nanodropper.

PURPOSE: 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). DESIGN: Prospective, noninferiority, parallel, multicenter, single-masked, active-controlled, randomized trial. PARTICIPANTS: Treatment-naïve subjects who were recently diagnosed with OAG and OHT at the Aravind Eye Care System. METHODS: 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. MAIN OUTCOME MEASURES: The IOP was the primary outcome measure. Secondary outcomes were resting HR, systolic BP (sBP), and diastolic BP (dBP). RESULTS: 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. CONCLUSIONS: Timolol microdrops appear to be as effective in ocular hypotensive action as conventional drops with a slightly attenuated effect on resting HR and BP. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

A Histomorphometric and Computational Investigation of the Stabilizing Role of Pectinate Ligaments in the Aqueous Outflow Pathway.

Murine models are commonly used to study glaucoma, the leading cause of irreversible blindness. Glaucoma is associated with elevated intra-ocular pressure (IOP), which is regulated by the tissues of the aqueous outflow pathway. In particular, pectinate ligaments (PLs) connect the iris and trabecular meshwork (TM) at the anterior chamber angle, with an unknown role in maintenance of the biomechanical stability of the aqueous outflow pathway, thus motivating this study. We conducted histomorphometric analysis and optical coherence tomography-based finite element (FE) modeling on three cohorts of C57BL/6 mice: "young" (2-6 months), "middle-aged" (11-16 months), and "elderly" (25-32 months). We evaluated the age-specific morphology of the outflow pathway tissues. Further, because of the known pressure-dependent Schlemm's canal (SC) narrowing, we assessed the dependence of the SC lumen area on varying IOPs in age-specific FE models over a physiological range of TM/PL stiffness values. We found age-dependent changes in morphology of outflow tissues; notably, the PLs were more developed in older mice compared to younger ones. In addition, FE modeling demonstrated that murine SC patency is highly dependent on the presence of PLs and that increased IOP caused SC collapse only with sufficiently low TM/PL stiffness values. Moreover, the elderly model showed more susceptibility to SC collapse compared to the younger models. In conclusion, our study elucidated the previously unexplored role of PLs in the aqueous outflow pathway, indicating their function in supporting TM and SC under elevated IOP.