Aqueous Humor Outflow Research Articles

Fibrosis and Src Signalling in Glaucoma: From Molecular Pathways to Therapeutic Prospects

Glaucoma, a leading cause of irreversible blindness, is characterised by progressive optic nerve damage, with elevated intraocular pressure (IOP) and extracellular matrix (ECM) remodelling in the lamina cribrosa (LC) contributing to its pathophysiology. While current treatments focus on IOP reduction, they fail to address the underlying fibrotic changes that perpetuate neurodegeneration. The Src proto-oncogene, a non-receptor tyrosine kinase, has emerged as a key regulator of cellular processes, including fibroblast activation, ECM deposition, and metabolism, making it a promising target for glaucoma therapy. Beyond its well-established roles in cancer and fibrosis, Src influences pathways critical to trabecular meshwork function, aqueous humour outflow, and neurodegeneration. However, the complexity of Src signalling networks remains a challenge, necessitating further investigation into the role of Src in glaucoma pathogenesis. This paper explores the therapeutic potential of Src inhibition to mitigate fibrotic remodelling and elevated IOP in glaucoma, offering a novel approach to halting disease progression.

Visualization of porcine and human aqueous humor outflow tract anatomies with transparency enhancement.

There is no established method for visualizing the three-dimensional (3D) structure of the aqueous humor outflow tract. This study attempted to visualize the 3D structures of porcine and human ocular tissues, particularly the aqueous humor outflow tract using a transparency reagent composed of 2, 2-thiodiethanol. Clinical and experimental. The porcine eyes were collected in Japan, and the human eyes were imported from the United States. The human eyes were obtained from a 64-year-old Caucasian woman, arriving 7 days after her death. The specimens were formalin-fixed upon arrival, fluorescently labeled, optically cleared using a transparency-enhancing reagent, and visualized using a confocal microscope. Both porcine and human eyes were visualized to the extent that the choroidal vessels were observed on gross examination. The aqueous humor outflow tract was clearly observed as a luminal structure in the porcine eye, mainly depicted by autofluorescence, and in the human eyes as a luminal structure continuing from the trabecular meshwork without fluorescence. Observations using transparency-enhancing technology enabled us to obtain 3D images useful for visualizing ocular tissues, especially the aqueous humor outflow tract.

Aqueous Angiography Guided Bent Ab Interno Needle Goniectomy in High versus Low Aqueous Humor Outflow Regions in POAG: A Pilot RCT.

Trabecular cutting minimally invasive glaucoma surgery like bent ab interno needle goniectomy (BANG) when performed in baseline aqueous angiography identified low aqueous humor outflow regions, results in greater success of intraocular pressure reduction. To study the efficacy of Bent Ab Interno Needle Goniectomy (BANG) in high versus low aqueous humor outflow (AHO) regions as determined by Aqueous Angiography(AA) in patients with primary open angle glaucoma (POAG). A prospective, single-centre, pilot, randomized control trial recruited 30 eyes of 30 patients of POAG and visually significant cataract (45-80y) and were randomised into two groups ("A": BANG performed in the high-flow regions and "B": BANG performed in the low-flow regions) of 15 each. AA was performed using indocyanine green dye (0.1%) to identify baseline high- and low-flow regions of the AHO pathways followed by BANG in these respective regions as per randomisation. Preoperative and postoperative data on IOP, number of antiglaucoma medications (AGMs) and any complications were noted over 6 months. Overall success was defined as achieving an IOP ≤15mm Hg and ≥6mm Hg at 6 months of follow-up with AGMs (qualified success) or without AGMs (complete success). AA revealed high-flow regions of AHO pathways in the nasal quadrant and low-flow regions of AHO pathways in the temporal quadrant in all 30 patients. Both groups had comparable demographic composition [group A age: 65.3±6.48y and male: female (14:1) and group B age: 64.6±7.08y and male: female (13:2)]. The mean preoperative IOPs [group A (17.27±3.43mm Hg); group B (17.60±5.42mm Hg)] (P=0.842) and mean postoperative IOP at 6 months [group A (15.6±4.98mm Hg); group B (13.13±2.29mm Hg)] (P=0.09) were similar. However, lower qualified success was seen in group A (40.00%) compared to group B (86.67%; P=0.021). Survival in Kaplan-Meier analysis was higher in group B (P=0.021). Complications were comparable in both groups. Short-term results of BANG in low-flow AHO regions show enhanced success compared to those in high-flow AHO regions. This study suggests that trabecular cutting minimally invasive glaucoma surgeries (like BANG) may be performed in baseline low-flow AHO regions (temporal quadrant) instead of the high-flow AHO (nasal quadrant) regions.

Self-generating electricity system driven by aqueous humor flow and trabecular meshwork contraction motion activated BCKa for glaucoma intraocular pressure treatment.

Primary open-angle glaucoma (POAG) is the most common form of glaucoma and the leading cause of irreversible vision loss and blindness worldwide. Intraocular pressure (IOP) is the only modifiable risk factor, and prompt treatment to lower IOP can effectively slow the rate of vision loss due to glaucoma. Trabecular meshwork (TM) cells can maintain IOP homeostasis by correcting and adjusting the resistance to aqueous humor outflow in response to sustained pressure changes. TM cells' function is reduced, and membrane ion channels are impaired in POAG. The dysfunction of Large conductance Ca2+-activated K+ (BKCa) plays a central role in the pathogenesis of POAG. In this work, we targeted MXene nanoparticles (MXene-RGD) with piezoelectric response to TM cells in a 3D model of glaucoma in vitro as well as in the rabbit Transient Ocular Hypertension (OHT) Model in vivo. MXene-RGD gives the TM electromechanical transfer properties, while the self-enhancing and self-generated electricity properties of the TM are determined by the aqueous humor flow rate and the size of the deformation of the TM. MXene-RGD is nontoxic, as illustrated by a cell toxicity study and histological examination. In a 3D in vitro model of high-pressure glaucoma, whole-cell patch-clamp confirmed that piezoelectric stimulation turns on BKCa, which reduces the volume of the cell. MXene-RGD was injected into the anterior chamber with minimal trauma, i.e., anterior chamber injection, and specifically targeted to TM cells. The OHT model in vivo confirmed the potential IOP-lowering ability of MXene-RGD. We evaluated the ion channels involved in the reduction of IOP by MXene-RGD by pre-treatment with a BKCa channel blocker (iberiotoxin, IbTX) and a voltage-gated Ca2+channel blocker (nifedipine). Quantitative qPCR analysis showed that MXene-RGD inhibited the upregulation of mRNA expression levels of the myofibroblast marker α-smooth muscle actin (α-SMA) and the inflammatory response marker interleukin-6 (IL-6) induced by IOP. Histology confirmed that MXene-RGD attenuated IOP-induced proliferation and collagen production in the TM. Taken together, we present for the first time a minimally invasive surgical approach for targeting TM cells for POAG by utilizing piezoresponse nanomaterials to target BKCa to repair or awaken the ability of TM cells to regulate IOP homeostasis on their own.

High Glucose-Induced Transcriptomic Changes in Human Trabecular Meshwork Cells.

Glaucoma is a leading cause of irreversible blindness, often associated with elevated intraocular pressure (IOP) due to trabecular meshwork (TM) dysfunction. Diabetes mellitus (DM) is recognized as a significant risk factor for glaucoma; however, the molecular mechanisms through which hyperglycemia affects TM function remain unclear. This study investigated the impact of high glucose on gene expression in human TM (HTM) cells to uncover pathways that contribute to TM dysfunction and glaucoma pathogenesis under diabetic conditions. Primary HTM cells were cultured under normoglycemic (5.5 mM) and hyperglycemic (30 mM) conditions for seven days, followed by mRNA sequencing (mRNA-seq) to identify differentially expressed genes, with quantitative PCR (qPCR) used for confirmatory analysis. STRING network analysis was performed to predict interactions among upregulated and downregulated proteins. mRNA-seq analysis revealed 25 significantly differentially expressed genes in high glucose conditions, including upregulated genes associated with oxidative stress, apoptosis, autophagy, immune response, and fibrosis. Notably, TXNIP was significantly upregulated, indicating increased oxidative stress and apoptosis in TM cells, while downregulation of autophagy-related genes, such as HSPA6 and LAMP3, suggests compromised protein quality control. Immune response genes, including CCL7 and CHI3L1, were upregulated, suggesting an inflammatory response to oxidative stress. Increased expression of fibrosis-related genes, such as SNAI1, FGF7, and KRT19, supports the hypothesis of ECM accumulation in diabetic conditions, potentially elevating IOP. Chronic hyperglycemia in diabetic patients could therefore lead to TM dysfunction, impair aqueous humor outflow, and elevate IOP, thereby increasing glaucoma risk. Targeting oxidative stress and fibrosis pathways offers therapeutic strategies to mitigate glaucoma progression in diabetic populations.

Association of Matrix Metalloproteinases Polymorphisms with Glaucoma Risk, Glaucoma Phenotype, and Response to Treatment with Selective Laser Trabeculoplasty or Latanoprost.

In open-angle glaucoma, the increase in intraocular pressure (IOP) is caused by an increased resistance to aqueous humour outflow in the trabecular meshwork. Since genetic variability of matrix metalloproteinase (MMP) genes may influence extracellular matrix remodelling, we investigated their association with glaucoma risk and/or response to treatment. The retrospective part of the study included patients with primary open-angle glaucoma and ocular hypertension (OHT); in the prospective part of the study, newly diagnosed patients with POAG or OHT were randomised to receive either latanoprost or selective laser trabeculoplasty (SLT) as the initial treatment. The reduction in IOP was measured 6 weeks after treatment. The following MMP single nucleotide polymorphisms were genotyped: MMP2 rs243865, rs243849, and rs7201; MMP3 rs3025058; MMP9 rs17576, rs17577, rs20544, and rs2250889; MMP14 rs1042704, rs1042704, and rs743257. Logistic regression was used to calculate odds ratios to assess the association between MMP polymorphism and risk of POAG or OHT, glaucoma phenotypes and response to treatment. Only carriers of the MMP3 rs3025058 TT genotype had a significantly higher risk of OHT, more advanced glaucoma, and a higher C/D ratio in the additive and dominant models. None of the investigated MMP polymorphisms were associated with response to treatment with latanoprost and SLT in our study population.

Application progress of micropulse wave transscleral laser treatment in glaucoma

Glaucoma is the leading cause of blindness worldwide, and reducing intraocular pressure is crucial to delaying its progression. This review aims to explore the application progress of micropulse wave transscleral laser treatment (mTLT) in the treatment of glaucoma. This article introduces the evolution of ciliary body destructive surgical methods, and focuses on the mechanism of mTLT in the treatment of glaucoma, including reducing aqueous humor production, increasing the uveoscleral pathway and trabecular meshwork pathway for aqueous humor outflow. At the same time, the indications, contraindications, procedures and parameter settings of mTLT, its application effects in different types of glaucoma, possible complications, repeatability, and factors affecting the effect are discussed, and a comparison is made with the traditional TSCPC. However, the exact mechanism of mTLT in reducing intraocular pressure still needs to be further explored and clarified, and its related parameter settings still require a large number of clinical observations and studies.

Latanoprostene bunod: the first nitric oxide-donating antiglaucoma medication.

Glaucoma is a chronic optic neuropathy that causes characteristic visual field defects and is considered one of the leading causes of irreversible vision loss worldwide. Lowering intraocular pressure is the only proven treatment for glaucoma. Medical therapy is usually the first-line treatment for open-angle glaucoma and ocular hypertension. Latanoprostene bunod ophthalmic drop 0.024% is a nitric oxide-donating prostaglandin F2α analog. It lowers the intraocular pressure via a dual mechanism of enhancing aqueous humor outflow through both the trabecular meshwork and uveoscleral pathways. Additionally, the nitric oxide component has shown promise in regulating ocular blood flow and promoting the survival of retinal ganglionic cells. Herein, the mechanism of action, efficacy, safety, and tolerability of the latanoprostene bunod and its effects on ocular blood flow are reviewed. Latanoprostene bunod has demonstrated strong efficacy and a favorable safety profile in both clinical trials and real-world studies. Given the promising results of latanoprostene bunod and advancements in drug delivery, topical fixed-combination and sustained-release formulations containing latanoprostene bunod and other agents targeting different intraocular pressure-lowering mechanisms may become available in the future.

Gender differences in canine anterior chamber dimensions: Potential implications for primary angle-closure glaucoma.

This study aimed to explore anatomical differences in the aqueous humor (AH) outflow pathway between male and female dogs using ultrasound biomicroscopy (UBM). Clinical data were collected from 30 eyes of 30 dogs (15 males: 10 right eyes, 5 left eyes; and 15 females: 7 right eyes, 8 left eyes) treated at the Veterinary Medical Teaching Hospital of Chungbuk National University, South Korea, between August 2018 and February 2024. The study conducted an in-depth UBM examination, specifically observing peripheral anterior chamber depth (ACD), geometric iridocorneal angle (ICA), and angle-opening distance (AOD) alongside measurements of ciliary cleft width (CCW), length (CCL), and area (CCA), and assessed the longitudinal fibers of ciliary muscle thickness (Lf-CMT) and the longitudinal and radial fibers of ciliary muscle thickness (LRf-CMT) for gender-based differences. The study identified a significant sex difference in peripheral ACD, with females displaying shallower depths compared to males, potentially clarifying the higher incidence of glaucoma in female dogs. No significant gender differences were found in ICA, AOD, CC parameters, or ciliary muscle parameters measurements. This research uncovered that peripheral ACD is significantly shallower in females than in males, potentially indicating a risk factor that could contribute to the development of primary angle-closure glaucoma.

Mitochondrial and Microtubule Defects in Exfoliation Glaucoma.

Exfoliation Syndrome (XFS) is an age-related systemic condition characterized by large aggregated fibrillar material deposition in the anterior eye tissues. This aggregate formation and deposition on the aqueous humor outflow pathway are significant risk factors for developing Exfoliation Glaucoma (XFG), a secondary open-angle glaucoma. XFG is a complex, multifactorial late-onset disease that shares common features of neurodegenerative diseases, such as altered cellular processes with increased protein aggregation, impaired protein degradation, and oxidative and cellular stress. XFG patients display decreased mitochondrial membrane potential and mitochondrial DNA deletions. Here, using Tenon Capsule Fibroblasts (TFs) from Normal (No Glaucoma) and XFG patients, we found that XFG TFs have impaired mitochondrial bioenergetics and increased reactive oxygen species (ROS) accumulation. These defects are associated with mitochondrial abnormalities as XFG TFs exhibit smaller mitochondria that contain dysmorphic cristae, with an increase in mitochondrial localization to lysosomes and slowed mitophagy flux. Mitochondrial dysfunction in the XFG TFs was associated with an increase in the dynamics of the microtubule cytoskeleton, decreased acetylated tubulin, and increased HDAC6 activity. Treatment of XFG TFs with a mitophagy inducer, Urolithin A, and a mitochondrial biogenesis inducer, NAD + precursor, Nicotinamide Ribose, improved mitochondrial bioenergetics and reduced ROS accumulation. Our results demonstrate abnormal mitochondria in XFG TFs and suggest that mitophagy inducers may represent a potential class of therapeutics for reversing mitochondrial dysfunction in XFG patients.

Physiological activation of liver X receptor provides protection against ocular inflammation in uveitic glaucoma

Virus-induced trabeculitis is considered a significant cause of uveitic glaucoma, being marked by a sudden increase in intraocular pressure and relatively mild inflammation in the anterior chamber of the eye. In previous proteome analyses of aqueous humor (AH) derived from Cytomegalovirus (CMV) uveitic glaucoma patients, we observed the liver X receptor (LXR) pathway to be among the most prominently activated canonical pathways. In the present study, we explored the role of the LXR pathway in the etiology of glaucoma in association with ocular inflammation. LXRα/β and ABCA1, the downstream targets of LXR, were distributed throughout the conventional AH outflow pathway of the human eye, and their increased levels in human trabecular meshwork cells in response to CMV infection and -lipopolysaccharide (LPS) treatment. Treatment with an LXR agonist (T091317) suppressed LPS-induced inflammation and this response was reversed under the deficiency of LXRα/LXRβ. Furthermore, in the rat endotoxin uveitis model, the LXR agonist significantly reduced infiltrating cells and expression of proinflammatory cytokines in the iris and retina. These results reveal upregulation of LXR-ABCA1 under inflammatory insult in the conventional AH outflow pathway, and activation of LXR exhibiting an anti-inflammatory effect, implying its essential physiological protective role in glaucoma associated with ocular inflammation.

Aqueous Humor Angiography.

Aqueous humor angiography, or aqueous angiography, is an anterior segment imaging technique capable of visualizing the conventional/trabecular aqueous humor outflow pathways. As a translational technique, it is applicable for in vivo imaging in living subjects and ex vivo imaging using whole-globe preparations or anterior segment perfusion setups. Excellent spatial and temporal resolution has enabled insights into the segmental distribution of aqueous humor outflow in physiological conditions as well as after trabecular bypass surgery. In this chapter, we thoroughly describe aqueous humor angiography in various experimental setups. The necessary materials for different settings and their application for in vivo and ex vivo experiments as well as notes on dye choice, dye sequences, and special considerations on performing aqueous humor angiography during surgery are presented.

Evaluation of Cross-Linked Actin Networks (CLANs) in Human Trabecular Meshwork Cells and Tissues.

Elevated intraocular pressure (IOP) is a major risk factor for the development and progression of glaucoma, the leading cause of irreversible vision loss and blindness. An overall increase in resistance to aqueous humor outflow causes sustained elevation in IOP. Glaucomatous insults in the aqueous humor outflow pathway, including the trabecular meshwork (TM), precede such chronic physiological changes in IOP. These insults include ultrastructural changes with excessive extracellular matrix deposition and actin cytoskeletal reorganization that leads to pathological stiffening of the ocular tissues. One of the most common cytoskeletal changes associated with TM tissue stiffness in glaucoma is the increased prevalence of cross-linked actin networks (CLANs) in cells of the trabecular meshwork (TM) and lamina cribrosa (LC). In glaucomatous cells, rearrangement of linear actin stress fibers leads to formation of polygonal arrays within the cytoplasm, resembling a geodesic dome-like structure, that we identified as CLANs. In addition to increased amounts of CLANs in POAG TM cells and tissues, we also discovered that glucocorticoid (GC) and TGFβ2 signaling pathways associated with the development of ocular hypertension (OHT) and glaucoma also induced CLANs in the TM. Despite a clear association, we are yet to completely understand the mechanisms involved in CLAN formation and their direct relevance to disease pathology. In this chapter, we will describe methods to identify and characterize CLANs using fluorescent microscopy in primary TM cell cultures, ex vivo perfusion cultured human anterior segments, and in situ in human donor eyes.

Time-Lapse Live-Cell Imaging Using Fluorescent Protein Sensors in Outflow Pathway Cells Under Fluid Flow Conditions.

The role of shear stress in regulating aqueous humor (AH) outflow and intraocular pressure (IOP) in the trabecular meshwork (TM) and Schlemm's canal (SC) of the eye is an emerging field. Shear stress has been shown to activate mechanosensitive ion channels in TM cells and induce nitric oxide production in SC cells, which can affect outflow resistance and lower IOP. Live-cell imaging using fluorescent protein sensors has provided real-time data to investigate the physiological relationship between fluid flow and shear stress in the outflow pathway cells. The successful application of time-lapse live-cell imaging in primary cultured cells has led to the identification of key cellular and molecular mechanisms involved in regulating AH outflow and IOP, including the role of autophagy and primary cilia as mechanosensors. This chapter presents a detailed protocol for conducting time-lapse live-cell imaging under fluid flow conditions in the outflow pathway cells.

Protocol for the Extraction and Characterization of Trabecular Meshwork Cell Cytoskeleton Fraction.

Among various cellular attributes modulating aqueous humor (AH) outflow through the trabecular pathway and eventually intraocular pressure, the involvement of actomyosin regulated cellular contraction and relaxation, cell-extracellular matrix adhesion and cell-cell junctions, and mechanotransduction are well recognized. Although various biological and pharmacological agent-modulated AH outflows were associated with altered actin cytoskeletal organization and cell adhesive interactions of trabecular meshwork (TM) cells, these changes were analyzed largely with a biased approach to examine the specific proteins, but there were very few efforts in examining them with hypothesis-free unbiased approach in their native state. Therefore, in this chapter, we describe a protocol tailored to characterize the cytoskeleton of TM cells. This simple protocol can be applied to identifying the differentially regulated TM cell cytoskeleton proteins under any given treatment condition in conjunction with quantitative proteomic analysis.

Effectiveness and biocompatibility of a novel Schlemm’s canal microstent for glaucoma management

To evaluate the effectiveness and biocompatibility of Wistend, a novel Schlemm’s canal (SC) microstent made of Nitinol designed to improve aqueous humor outflow. New Zealand white (NZW) rabbits were divided into blank, sham-operated and Wistend groups. ICare® Tonovet Plus®, swept-source optical coherence tomography (SS-OCT), slit lamp biomicroscopy, retinal camera and scanning electron microscopy (SEM) were used for preoperative and postoperative observations. Hematoxylin and Eosin (H&E) tissue staining was adopted for biocompatibility. A significant difference in intraocular pressure (IOP) between the Wistend group and the control groups was observed during the six-month follow-up. SS-OCT identified arc line internal reflections within the SC in the anterior chamber angle. Conjunctival congestion and edema gradually diminished in the early stages. No corneal vascularization, no anterior chamber inflammatory response and no significant tissue reactions were noted in any groups. SEM showed the Wistend’s windows and orifices remained clear, encircled by minimal incidental ocular tissue and free from blockage. Histopathological examination revealed no discernible differences between the Wistend-implanted and sham-operated eyes. These in vivo studies demonstrate the effectiveness and biocompatibility of the microstent. Our findings suggest a promising potential for Wistend in significantly reducing IOP and effectively facilitating the outflow of aqueous humor.

Green-Light-Triggered and Self-Calibrated Cascade Release of Nitric Oxide and Carbon Monoxide for Synergistic Glaucoma Therapy.

Glaucoma is an optic degenerative neuropathy that is driven by a vicious cycle of oxidative stress and mechanical stress. Current clinical treatments aim exclusively at alleviating mechanical stress by reducing the intraocular pressure (IOP). With the unattended oxidative stress, recurrence and deterioration of mechanical stress are inevitable. Nitric oxide (NO) and carbon monoxide (CO) are endogenous gaseous signaling molecules for vasodilation and anti-inflammation, respectively. Mounting evidence suggests an intricate interplay between NO and CO to mediate their biological roles, like how it takes two to dance a waltz. This leads to the concept of "gas waltz therapy" for glaucoma, in which NO is released to reduce IOP and stoichiometric CO is coreleased to suppress oxidative stress. CND570 is the first phototriggered cascade NO/CO donor, to the best of our knowledge. Notably, the release of NO/CO is accompanied by the concomitant release of a rhodamine dye whose bright fluorescence is harnessed as a convenient calibration mechanism of the gas release profile. CND570 exhibits excellent transcorneal permeability and reaches the target aqueous humor outflow pathway. Further, green-light irradiation triggers release of CO and NO in the eye tissue of glaucoma mice. NO and CO could promote the upregulation of soluble guanylate cyclase (sGC) in both in vitro and in vivo models. Notably, CND570 treatment significantly reduces the oxidative stress associated with glaucoma. NO/CO-based gas waltz therapy is a promising new avenue for glaucoma treatment.

Corticosteroids and glaucoma: How do treatments trigger ocular nerve damage? - A systematic literature review

Corticosteroids are steroid hormone derivatives produced by the adrenal glands. Corticosteroids in the health sector have been widely utilized as anti-inflammatory agents because of their strong and rapid effects. This study aimed to identify the impact of long-term corticosteroid use on eye damage. This study uses a systematic literature review, which is guided by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) to the article screening process. The data of this study, in the form of demographic variables, route of administration, steroid type, comorbidities, and patient risk factors, were descriptively analyzed. As a result, 15 of the 22 articles were selected for analysis. Chronic corticosteroid administration may precipitate optic neuropathy, manifesting as glaucoma, which is characterized by progressive structural degeneration of retinal ganglion cells (RGCs) and concomitant visual function deterioration. The locus of primary pathological insult in glaucomatous conditions is the optic nerve head, specifically at the optic disc. This anatomical site is notable for the abrupt 90-degree angular deviation of RGC axons as they transition from the retinal nerve fiber layer to their trajectory within the optic nerve proper. The use of corticosteroids can damage ocular nerve tissue through an increase in intraocular pressure (IOP) beyond 21 mmHg. This increase in IOP is due to changes in the microstructure of the trabeculum webbing, resulting in increased obstruction to the outflow of aqueous humor.

Delayed onset Spontaneous Hyphema after OMNI® Surgical System

Minimally invasive glaucoma surgery (MIGS) offers options for glaucoma treatment that have generally improved safety profiles compared with filtering surgery. MIGS vary in design and procedure, but all angle-based MIGS function by bypassing or removing aqueous humor outflow resistance at the level of the trabecular meshwork. This can lower intraocular pressure but also remove the blood-aqueous barrier. Most studies of MIGS report on relatively short-term safety, but awareness of potential long-term complications is critical for optimal patient management. This case report describes a patient with recurrent and refractory delayed onset spontaneous hyphema after OMNI procedure. To the best of our knowledge, this is the first case report describing this complication of the OMNI surgical system.

Low Intraocular Pressure Induces Fibrotic Changes in the Trabecular Meshwork and Schlemm's Canal of Sprague Dawley Rats.

Continuous artificial aqueous humor drainage in the eyes of patients with glaucoma undergoing trabeculectomy likely exerts abnormal shear stress. However, it remains unknown how changes in intraocular pressure (IOP) can affect aqueous humor outflow (AHO). Here, we induced and maintained low intraocular pressure (L-IOP) in healthy Sprague Dawley (SD) rats by puncturing their eyes using a tube (200-µm diameter) for 2 weeks. After the rats were euthanized, their eyes were removed, fixed, embedded, stained, and scanned to analyze the physiological and pathological changes in the trabecular meshwork (TM) and Schlemm's canal (SC). We measured SC parameters using ImageJ software and assessed the expression of various markers related to flow shear stress (KLF4), fibrosis (TGF-β1, TGF-β2, α-SMA, pSmad1/5, pSmad2/3, and fibronectin), cytoskeleton (integrin β1 and F-actin), diastolic function (nitric oxide synthase and endothelial nitric oxide synthase [eNOS]), apoptosis (cleaved caspase-3), and proliferation (Ki-67) using immunofluorescence or immunohistochemistry. L-IOP eyes showed a larger SC area, higher eNOS expression, and lower KLF4 and F-actin expression in the TM and SC (both P < 0.05) than control eyes. The aqueous humor of L-IOP eyes had a higher abundance of fibrotic proteins and apoptotic cells than that of control eyes, with significantly higher TGF-β1, α-SMA, fibronectin, and cleaved caspase-3 expression (all P < 0.05). In conclusion, a persistence of L-IOP for 2 weeks may contribute to fibrosis in the TM and SC and might be detrimental to conventional AHO in SD rat eyes. Clinicians should consider that aberrant shear force induced by aqueous humor fluctuation may damage AHO outflow channel when treating patients.