Elevated Pressure Research Articles

Dexamethasone implant in naive versus refractory patients with diabetic macular edema: a Meta-analysis.

To evaluate the efficacy and safety of the intravitreal dexamethasone implant in naive and refractory patients with diabetic macular edema (DME). PubMed, Embase, Web of Science, and Medline databases were searched. The main outcomes were best-corrected visual acuity (BCVA) and central retinal thickness (CRT). The secondary outcomes included mean number of injections, intraoperative or postoperative complications including intraocular pressure (IOP) elevation and cataract. Ten comparative studies involving a total of 1000 DME eyes including 402 naive eyes and 598 refractory eyes were selected. The postoperative BCVA in the naive group was significantly better than in the refractory group [mean difference (MD) -0.11, 95% confidence interval (CI) -0.17 to -0.05, P=0.0003; MD 8.69, 95%CI 5.08 to 12.30, P<0.00001)]. Additionally, the naive group got greater improvement of BCVA change as well as more gains of BCVA letters than the refractory group [MD 7.71, 95%CI 2.02 to 13.40, P=0.008; odds ratio (OR) 2.99, 95%CI 2.05 to 4.37, P<0.00001]. The subgroup analysis revealed that the naive group had significantly higher BCVA gains of ≥5, ≥10, and ≥15 letters compared to the refractory group (P=0.002, 0.0001, 0.003, respectively). No significant difference was detected between the two groups in either postoperative CRT (MD -22.36, 95%CI -46.39 to 1.66, P=0.07) or the overall mean number of injections (MD -0.08, 95%CI -0.38 to 0.22, P=0.61). Intraoperative and postoperative complications including the elevation of IOP (OR 0.47, 95%CI 0.20 to 1.13, P=0.09) and cataract (OR 1.78, 95%CI 0.97 to 3.24, P=0.06) showed no significant differences between the two groups during the follow-up time. Intravitreal dexamethasone implants for DME can improve anatomical and functional outcomes in both naive and refractory eyes and have a well-acceptable safety profile. Moreover, naive eyes maintain better visual outcomes than refractory eyes. It provides further evidence of better visual response when used for naive eyes as first-line therapy.

Laser-induced plasma analysis of ammonia-oxygen and ammonia-oxygen-enriched-air flames at elevated pressures

This study employed Laser-induced breakdown spectroscopy (LIBS) to measure the fuel-oxidizer ratio (FOR) of ammonia combustion with oxygen-enriched air and pure oxygen flames at elevated pressures (100 - 300 kPa). The correlations between the spectral line intensity ratios of nitrogen (N), hydrogen (H), oxygen (O), and equivalence ratio were used to quantify the FOR of flames at various pressures. The effect of pressure on the stability and precision of the calibration profiles for the elemental intensity ratios in flames was investigated. It was observed that the H/O correlation decreases with pressure increase for both ammonia flames. N/O correlations decrease with elevated pressure for the ammonia-oxygen flame. Furthermore, the nitrogen (NII) spectral emission lines at 568 nm and 595 nm were used to estimate the plasma temperature, while the hydrogen (Hα) line at 656 nm was used for electron number density measurements.

Flash Flow-Induced Crystallization of Poly(l-lactide) under Elevated Pressure during Industrial-Scale Injection Molding Revealed by Time-Resolved Synchrotron X-ray Scattering

Flash Flow-Induced Crystallization of Poly(<scp>l</scp>-lactide) under Elevated Pressure during Industrial-Scale Injection Molding Revealed by Time-Resolved Synchrotron X-ray Scattering

Dynamics of Blood Lipids Before, During, and After Diurnal Fasting in Inactive Men: Quasi-Experimental Study.

There is a lack of investigation into the dynamics of blood lipids before, during, and after diurnal fasting, especially in inactive men. This study determined dynamic changes in blood lipids in inactive men before, during, and after they underwent diurnal fasting. A total of 44 young men aged a mean 27.6 (SD 5.8) years were recruited to evaluate their habitual physical activity and diet using a questionnaire developed for this study. Body composition was evaluated using a bioelectrical impedance analysis machine (Tanita BC-980). An 8-ml blood sample was collected to evaluate blood lipids and glucose. All measurements were taken 2-3 days before Ramadan, during Ramadan (at week 2 and week 3), and 1 month after Ramadan. A 1-way repeated measures ANOVA was used to compare the measured variables before, during, and after the month of Ramadan. When a significant difference was found, post hoc testing was used. Differences were considered significant at P<.05. There was a significant reduction in low-density lipoprotein during Ramadan compared to before and after Ramadan (83.49 mg/dl at week 3 vs 93.11 mg/dl before Ramadan [P=.02] and 101.59 mg/dl after Ramadan [P=.007]). There were significant elevations in fasting blood glucose (74.60 mmol/L before Ramadan vs 81.52 mmol/L at week 3 [P=.03] and 86.51 mmol/L after Ramadan [P=.01]) and blood pressure (109 mm Hg before Ramadan vs 114 mm Hg after Ramadan; P=.02) reported during and even after the month of Ramadan, although both fasting blood glucose and blood pressure were within normal levels. Ramadan fasting could be an independent factor in reducing low-density lipoprotein. Further investigations are encouraged to clarify the impact of diurnal fasting on blood lipids in people with special conditions.

Metabolic adaptations of Shewanella eurypsychrophilus YLB-09 for survival in the high-pressure environment of the deep sea.

Elucidation of the adaptation mechanisms and survival strategies of deep-sea microorganisms to extreme environments could provide a theoretical basis for the industrial development of extreme enzymes. There is currently a lack of understanding of the metabolic adaptation mechanisms of deep-sea microorganisms to high-pressure environments. The objective of this study was to investigate the metabolic regulatory mechanisms enabling a strain of the deep-sea bacterium Shewanella eurypsychrophilus to thrive under high-pressure conditions. To achieve this, we used nuclear magnetic resonance-based metabolomic and RNA sequencing-based transcriptomic analyses of S. eurypsychrophilus strain YLB-09, which was previously isolated by our research group and shown to be capable of tolerating high pressure levels and low temperatures. We found that high-pressure conditions had pronounced impacts on the metabolic pattern of YLB-09, as evidenced by alterations in energy, amino acid, and glycerolipid metabolism, among other processes. YLB-09 adapted to the high-pressure conditions of the deep sea by switching from aerobic intracellular energy metabolism to trimethylamine N-oxide respiration, altering the amino acid profile, and regulating the composition and the fluidity of cell membrane. The findings of our study demonstrate the capacity of microorganisms to alter their metabolism in response to elevated pressure, thereby establishing a foundation for a more profound understanding of the survival mechanisms of life in high-pressure environments.

Symposium Highlight: PHYSIOLOGY AND FUNCTIONAL PATHOLOGY OF THE LYMPHATIC SYSTEM WITH IMPLICATIONS FOR THE FONTAN PATIENT

Contractile function of the collecting lymphatic vessels depend on smooth muscle cells, one-way valves, surrounding tissues, and regulation by the autonomic nervous system. The potentially deleterious effects of the Fontan procedure and elevated central venous pressure on lymphatic function leading to life-threatening complications are described. Presented at the 2023 ISL International Congress of Lymphology, Genoa, Italy in a special symposium on central and regional lymphatic system in health and disease.

Effects of hemodynamic load on cardiac remodeling in fish and mammals: the value of comparative models.

The ability of the vertebrate heart to remodel enables the cardiac phenotype to be responsive to changes in physiological conditions and aerobic demand. Examples include exercise-induced cardiac hypertrophy, and the significant remodeling of the trout heart during thermal acclimation. Such changes are thought to occur in response to a change in hemodynamic load (i.e. the forces that the heart must work against to circulate blood). Variations in hemodynamic load are caused by either a volume overload (high volume of blood returning to the heart, impairing contraction) or a pressure overload (elevated afterload pressure that the heart must contract against). The changes observed in the heart during remodeling are regulated by multiple cellular signaling pathways. The cardiac response to these regulatory mechanisms occurs across levels of biological organization, affecting cardiac morphology, tissue composition and contractile function. Importantly, prolonged exposure to pressure overload can cause a physiological response - that improves function - to transition to a pathological response that causes loss of function. This Review explores the role of changes in hemodynamic load in regulating the remodeling response, and considers the cellular signals responsible for regulating remodeling, incorporating knowledge gained from studying biomedical models and comparative animal models. We specifically focus on the renin-angiotensin system, and the role of nitric oxide, oxygen free radicals and transforming growth factor beta. Through this approach, we highlight the strong conservation of the regulatory pathways of cardiac remodeling, and the specific conditions within endotherms that may be conducive to the development of pathological phenotypes.

A role for cross-linking proteins in actin filament network organization and force generation

The high turgor pressure across the plasma membrane of yeasts creates a requirement for substantial force production by actin polymerization and myosin motor activity for clathrin-mediated endocytosis (CME). Endocytic internalization is severely impeded in the absence of fimbrin, an actin filament crosslinking protein called Sac6 in budding yeast. Here, we combine live-cell imaging and mathematical modeling to gain insights into the role of actin filament crosslinking proteins in force generation. Genetic manipulation showed that CME sites with more crosslinking proteins are more effective at internalization under high load. Simulations of an experimentally constrained, agent-based mathematical model recapitulate the result that endocytic networks with more double-bound fimbrin molecules internalize the plasma membrane against elevated turgor pressure more effectively. Networks with large numbers of crosslinks also have more growing actin filament barbed ends at the plasma membrane, where the addition of new actin monomers contributes to force generation and vesicle internalization. Our results provide a richer understanding of the crucial role played by actin filament crosslinking proteins during actin network force generation, highlighting the contribution of these proteins to the self-organization of the actin filament network and force generation under increased load.

Elevated Trans-mitral Pressure Gradient Predicts Surgery in Young People with Moderate-Severe Rheumatic Mitral Regurgitation.

Mitral regurgitation (MR) is the most common lesion in children with rheumatic heart disease (RHD). Progression of RHD results in the need for surgical intervention, the timing of which is dictated by left ventricular dilatation and the onset of heart failure symptoms. We sought to determine whether elevation in trans-mitral pressure gradient (TMPG) in those with moderate or severe rheumatic MR without significant mitral stenosis (MS) could predict the need for future surgical intervention. Echocardiographic studies were reviewed for 116 children and young people with moderate or severe rheumatic MR. Those with significant mitral stenosis or concurrent aortic valve disease were excluded. Trans-mitral pressure gradient was measured at baseline and details of mitral valve surgical intervention were retrieved from a registry database. Time to future surgery (up to six years) was compared between those with TMPG < 5mmHg and TMPG ≥ 5mmHg. Survival curves demonstrated an increased risk of surgery for those with TMPG ≥ 5mmHg with Cox proportional regression analysis providing a hazard ratio of 5.8. The proportion free from mitral valve surgery at one year for the TMPG < 5mmHg group was 0.94 (95% CI 0.86-0.97), compared to 0.62 (95% CI 0.42-0.77) in the ≥ 5mmHg group. Trans-mitral pressure gradient is a strong predictor of future mitral valve surgery in children and young people with significant rheumatic MR without MS. This non-invasive measure could be used to signal the need for more aggressive monitoring in order to optimize the timing of intervention.

Numerical investigation of the flow characteristics inside a supersonic vapor ejector

Integrating a vapor ejector with an air-cooled absorption cooling system (ACS) requires understanding how the ejector responds to varying condenser conditions and how the geometrical parameters affect the system's performance. This study provides a numerical investigation of the flow characteristics inside supersonic vapor ejectors. The primary objectives were identifying the best nozzle design for ACS and explaining how the secondary flow responds to different back pressures. The developed model was validated against experimental data and a one-dimensional model. Despite exhibiting increased flow fluctuations, the convex nozzle achieved an entrainment ratio of 0.4. This value was 4.9 % and 7 % higher than the values obtained by the straight and the concave nozzles, respectively. In contrast, the concave nozzle exhibits better flow stability and pressure recovery, which are considered appealing for the air-cooled ACS. The straight nozzle emerged as a balanced alternative, offering moderate entrainment alongside favorable flow stability. Moreover, secondary flow behavior at different operating modes was elaborated. Secondary flow choked at back pressures between 60–70 kPa, indicating optimal entrainment. However, at 75–80 kPa, while the secondary flow was entrained, it failed to reach sonic speed due to high-pressure waves, resulting in the sub-critical condition. Further increases in back pressure to 85–90 kPa induced back-flow due to elevated local static pressure. Mach number profiles at the mixing tube entrance remained consistent under critical operation but deviated post-critical back pressure, reflecting altered flow characteristics downstream of the mixing tube. Such elaboration of flow dynamics within ejectors paves the way for innovative designs of vapor ejectors, potentially developing ACS.

Economic Burden Associated with Pulmonary Arterial Hypertension in the United States.

Pulmonary arterial hypertension (PAH) is a progressive disease characterized by elevated pressure in the pulmonary arteries, commonly resulting in right heart failure. PAH is associated with a high economic burden throughout the duration of the disease. This retrospective cohort study of the Milliman Contributor Health Source Data, the Medicare 100% Research Identifiable Files, and the Merative Marketscan® Commercial dataset between 2018 and 2020 identified adult patients with prevalent PAH based on the earliest qualifying diagnosis date or medication date ('index date') between January 1, 2019 and November 30, 2020. Outcomes were assessed using patient data from index date through the earliest of end of enrollment, end of data, or death (Medicare fee-for-service [FFS] only). All-cause and PAH-related medical and pharmacy costs per-patient per-month (PPPM) and healthcare resource utilization per 1000 patients were summarized. The study included 11,670 Medicare FFS, 1021 Medicare Advantage, 274 Medicaid, and 1174 commercially insured patients in the US. The annual national burden to payers was estimated to be US$3.1 billion. The PPPM payer costs ranged from US$6500 to US$14,742; out-of-pocket (OOP) costs ranged from US$341 to US$907 PPPM. Inpatient utilization rate ranged from 435 to 770 per 1000 patients for all-cause admissions and from 15 to 58 per 1000 patients for PAH-related admissions. This study demonstrates that PAH continues to be associated with a high economic burden and healthcare resource utilization across all payer types within the US healthcare system.

Research progress of retinal neuroprotective drugs for glaucoma

Glaucoma is a neural degenerative disease characterized by progressive loss of retinal ganglion cells, resulting in irreversible visual field loss, low vision, and total blindness. Despite the fact that the pathological elevation of intraocular pressure is a major risk factor for glaucoma, it is imperative to develop therapies that can prevent and block retinal ganglion cell injury and apoptosis in addition to reducing intraocular pressure. Drug therapy is the primary treatment for glaucoma in most clinical cases. This article provides reference information for the clinical treatment of glaucoma by summarizing and analyzing the medications that have direct optic nerve protection in clinical or preclinical trials, based on the most recent research results from both domestic and international studies.

Brain hypoxia and metabolic crisis are common in patients with acute brain injury despite a normal intracranial pressure

Patients with acute brain injury are vulnerable to secondary deterioration, which may go undetected by traditional monitoring. However, multimodal neuromonitoring of brain tissue oxygen tension (PbtO2) and energy metabolism may be able to detect such episodes. We report a retrospective, observational study of 94 patients with aneurysmal subarachnoid haemorrhage (SAH) or traumatic brain injury (TBI) who underwent multimodal neuromonitoring during admission. We examined the co-occurrence of pathological neuromonitoring values: elevated intracranial pressure (ICP, > 20 mmHg), inadequate cerebral perfusion pressure (CPP, < 60 mmHg), brain hypoxia (PbtO2 < 20 mmHg), and metabolic crisis (lactate/pyruvate ratio > 40 and a glucose level < 0.2 mmol/L in cerebral microdialysate). Mixed effects linear regression demonstrated significant associations between abnormal ICP/CPP, cerebral hypoxia and metabolic crisis. However, brain hypoxia occurred in 40% and 31% of observations in patients with SAH and TBI, respectively, despite normal concurrent values of ICP. Similarly, metabolic crisis was observed in 8% and 16% of measurements for SAH and TBI, respectively, despite a normal ICP. The pattern was identical for CPP. In conclusion, although all neuromonitoring variables are interrelated, brain hypoxia and metabolic crisis are common despite an absence of abnormalities in conventional monitoring. Multimodal neuromonitoring may help identify such episodes and guide individualised treatment.

Lymphatic magnetic resonance imaging abnormalities in children with repaired tetralogy of Fallot.

Tetralogy of Fallot patients face an elevated risk of developing chylothorax and pleural effusions post-surgery. This patient group exhibits risk factors known to compromise the lymphatic system, such as elevated central venous pressure, pulmonary flow changes, and hypoxia. This study investigates the morphology and function of the lymphatic system in tetralogy of Fallot patients through lymphatic magnetic resonance imaging and near-infrared fluorescence imaging, respectively. Post-repair tetralogy of Fallot patients aged 6-18 years were recruited, along with age and gender-matched controls. Magnetic resonance imaging was used to assess the morphology of the thoracic lymphatic vessels and the thoracic, while near-infrared fluorescence imaging was used to assess lymphatic activity utilising lymph rate, velocity, and pressure. Nine patients and 10 controls were included. Echocardiography revealed that 2/3 of the patients had moderate-severe pulmonary regurgitation, while none displayed signs of elevated central venous pressure. Magnetic resonance imaging identified three patients with type 3 (out of 4 types) lymphatic abnormalities, while controls had none. The thoracic ducts showed severe (one patient) and moderate (one patient) tortuosity. Mean thoracic duct diameters were 3.3 mm ±1.1 in patients and 3.0 mm ± 0.8 in controls (p-value = 0.53). Near-infrared fluorescence imaging revealed no anomalous patterns. Despite no presence of clinical lymphatic disease, 3/9 of the repaired tetralogy of Fallot patients exhibited lymphatic morphological abnormalities. The significance of these anomalies remains uncertain currently. Further research is needed to determine whether these lymphatic alterations in this patient cohort are a result of congenital malformations, haemodynamic shifts, or prenatal and early-life saturation levels.

Deep learning from head CT scans to predict elevated intracranial pressure.

Elevated intracranial pressure (ICP) resulting from severe head injury or stroke poses a risk of secondary brain injury that requires neurosurgical intervention. However, currently available noninvasive monitoring techniques for predicting ICP are not sufficiently advanced. We aimed to develop a minimally invasive ICP prediction model using simple CT images to prevent secondary brain injury caused by elevated ICP. We used the following three methods to determine the presence or absence of elevated ICP using midbrain-level CT images: (1) a deep learning model created using the Python (PY) programming language; (2) a model based on cistern narrowing and scaling of brainstem deformities and presence of hydrocephalus, analyzed using the statistical tool Prediction One (PO); and (3) identification of ICP by senior residents (SRs). We compared the accuracy of the validation and test data using fivefold cross-validation and visualized or quantified the areas of interest in the models. The accuracy of the validation data for the PY, PO, and SR methods was 83.68% (83.42%-85.13%), 85.71% (73.81%-88.10%), and 66.67% (55.96%-72.62%), respectively. Significant differences in accuracy were observed between the PY and SR methods. Test data accuracy was 77.27% (70.45%-77.2%), 84.09% (75.00%-85.23%), and 61.36% (56.82%-68.18%), respectively. Overall, the outcomes suggest that these newly developed models may be valuable tools for the rapid and accurate detection of elevated ICP in clinical practice. These models can easily be applied to other sites, as a single CT image at the midbrain level can provide a highly accurate diagnosis.

Factors Associated with Retinal Microvasculature Dropout Induced by Elevation of Intraocular Pressure in Primary Open-Angle Glaucoma.

To investigate the risk factors related to decrease in vessel density (VD) observed in primary open-angle glaucoma (POAG), due to acute increase in intraocular pressure (IOP) by an ophthalmodynamometer (OPD). This cross-sectional study involved 42 eyes of participants (22 Controls and 20 POAG patients) that underwent optical coherence tomography angiography (OCT-A) to assess VD in the peripapillary region in three examination sets: primary gaze position (1), 25-degree adduction (2) and 25-degree adduction with OPD compression (3). Individual relationships between IOP levels and changes in the superficial complex VD were evaluated after image processing and exclusion of large retinal vessels. Multivariable regression analysis was used to verify factors associated with differences in VD induced by IOP elevation. A significant increase in IOP was induced by OPD compression during adduction (mean ± SD, Control: + 13.8 ± 2.8; POAG: + 13.4 ± 2.1mmHg). Only during IOP elevation (set 3), a significant VD decrease was observed both in POAG eyes (p = 0.008) and controls (p = 0.022). Baseline IOP (p = 0.022), maximum IOP (p = 0.003), and scleral rigidity (p = 0.029) were significantly associated with VD decreases in eyes with POAG. No changes were observed in VD during adduction gaze exclusively. Acute IOP elevation induced with OPD, but not adduction gaze, decreased peripapillary VD measured with OCT-A imaging. IOP levels and scleral rigidity significantly affected VD reduction in POAG patients. Thus, high scleral rigidity may decrease the ability of the globe to dampen the well-known effects of IOP fluctuation on glaucoma onset and progression. What is known Decrease vascular density in the peripapillary retina was associated with POAG, but factors related to the vascular response to elevated IOP are unexplored. What is new OCT-A quantification shows decreases in vascular density of the superficial layers of the peripapillary retina during an acute elevation in IOP. High IOP levels and scleral rigidity significantly affected vascular density reduction in POAG patients.

Non-Invasive Muscle Metabolism Assessment with Near-Infrared Spectroscopy and Electrical Muscle Stimulation

Background: Muscle biopsy, the gold standard for assessing muscle aerobic capacity, is an invasive procedure. Noninvasive alternatives, such as 31-phosphorus magnetic resonance spectroscopy (31P-MRS) and near-infrared spectroscopy (NIRS), provide valuable insights, with NIRS providing superior time resolution and ease of use compared with 31P-MRS. Objectives: This study aimed to evaluate muscle metabolism using a 6 s muscle contraction phase with electrical muscle stimulation (EMS) and to assess the impact of EMS on exercise performance under hyperbaric conditions with elevated oxygen pressure. Methods: This study included nine male participants (21 ± 2 years) who underwent 5 min of EMS on the forearm flexor muscle group, with muscle oxygen dynamics assessed using NIRS. For statistical analysis, the mean values between groups were assessed using paired t-tests, and associations were evaluated using Pearson’s correlation coefficient. Results: Spontaneous blood flow interruption during EMS-induced muscle activity indicated the potential for assessing muscle metabolism without disrupting external blood flow. A significant negative correlation was observed between oxygen consumption and changes in oxygenated hemoglobin levels during muscle activity under hyperbaric conditions. Conclusions: This study demonstrates that skeletal muscle metabolism can be measured using a brief 6 s quantitative EMS. Furthermore, hyperbaric exercise appears to enhance aerobic capacity by increasing the rate and availability of oxygen consumption during exercise.

Sensitivity Analysis of Depth-Controlled Oriented Perforation in Horizontal Wells Based on the 3D Lattice Method

The main method used to exploit unconventional oil and gas reservoirs involves multi-cluster perforation combined with hydraulic fracturing in horizontal wells. However, as the use of this technology has expanded, challenges like reduced perforation efficiency and elevated fracture initiation pressure have surfaced. The depth-controlled oriented perforation technique helps achieve uniform fracture initiation, enhance efficiency, and lower initiation pressure. In this study, a hydraulic fracturing fluid–solid coupling model at the perforation scale was established using the 3D lattice method to compare the near-wellbore fracture morphologies of depth-controlled oriented perforation, spiral perforation, and oriented perforation. Additionally, this study analyzes the effects of injection rate, reservoir elastic modulus, and horizontal stress difference on the fracture morphology and initiation pressure of depth-controlled oriented perforation. This study clarifies the applicability of depth-controlled oriented perforation in different types of reservoirs for the first time. The results indicate that intermediate fractures between spiral and oriented perforations are hindered, while depth-controlled oriented perforation ensures uniform fracture initiation. In the injection rate range of 0.144 to 0.360 L/min, an increase in injection rate accelerates the rise of fluid pressure within the perforations, leading to an increase in fracture initiation pressure. Therefore, excessively high injection rates are unfavorable for fracture initiation. Through depth-controlled oriented perforation, long and singular fractures can be formed in reservoirs with significant horizontal stress differences and high elastic moduli.

Safety and Efficacy of Metformin for Idiopathic Intracranial Hypertension. A U.S-Based Real-World Data Retrospective Multicenter Cohort Study.

Idiopathic intracranial hypertension (IIH) remains a challenging condition to manage, with limited therapeutic options. This study investigated the potential of metformin as a novel treatment for IIH, exploring its effects on disease outcomes and safety profile. We conducted a retrospective cohort study using the TriNetX database, analyzing data from 2009 to August 2024. Patients diagnosed with IIH were included, with exclusions for other causes of elevated intracranial pressure and pre-existing diabetes. Propensity score matching was employed to balance cohorts according to age, sex, race, ethnicity, Hemoglobin A1C, and baseline body mass index (BMI) at the time of metformin initiation. Outcomes were assessed at various follow-up points up to 24 months. Our study initially comprised 1,268 patients in the metformin group and 49,262 in the control group, with notable disparities in several parameters. Post-matching, both cohorts were refined to 1,267 patients each after matching with metformin group. Metformin-treated patients showed significantly lower risks of papilledema, headache, and refractory IIH status at all follow-up points (p<0.0001). The metformin group also had reduced rates of therapeutic spinal punctures and acetazolamide continuation. BMI reductions were more pronounced in the metformin group, with significant differences observed from 6 months onward (p<0.0001). Notably, metformin's beneficial effects persisted independently of BMI changes. The safety profile of metformin was favorable, with no significant differences in adverse events compared to the control group which did not receive metformin during the study timeframe. Our study provides evidence for metformin's potential as a disease-modifying therapeutic approach in IIH, demonstrating improvements across multiple outcomes. The benefits appear to extend beyond weight loss, suggesting complex mechanisms of action. These findings warrant further investigation through prospective clinical trials to establish metformin's role in IIH management and explore its underlying therapeutic mechanisms.

Optic Nerve Head in Case of Increased Intraocular Pressure, High Intracranial Pressure and Increased Intracranial Pressure with Simultaneous Intraocular Pressure

The optic nerve, as part of the central nervous system, is surrounded by meninges and cerebrospinal fluid (CSF). This review discusses the effects of increased intraocular pressure (IOP), elevated intracranial pressure (ICP), and the simultaneous rise in both pressures on the optic nerve head (ONH). Increased IOP, caused by the balance of aqueous humor production and drainage, can lead to glaucomatous optic neuropathy, particularly through mechanical and ischemic damage to the lamina cribrosa. Elevated ICP, characterized by increased CSF pressure, can result in optic nerve edema, impairing axonal transport and blood flow. The complex interactions between IOP and ICP are critical for understanding their combined impact on ONH deformation and glaucomatous damage. It is essential to consider both pressures in clinical evaluations and treatment strategies for optic nerve-related diseases. Recent studies suggest that both IOP and ICP influence the optic nerve head morphology and pathology, highlighting the importance of comprehensive management approaches. Further research is needed to elucidate the intricate dynamics of IOP and ICP in the pathogenesis of optic nerve diseases.