Schlemm's Canal Research Articles

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.

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.

Nanotubules and Cellular Communication in Trabecular Meshwork Cells.

Glaucoma causes dysfunction to tissues located in the anterior and posterior eye. In the anterior eye, the trabecular meshwork (TM) is the site of pathogenesis, where decreased TM cell numbers and alterations to the amount and composition of extracellular matrix hinder outflow of aqueous humor fluid from the anterior chamber. This causes intraocular pressure (IOP) elevation. Elevated IOP, a main risk factor for primary open-angle glaucoma, damages the axons of retinal ganglion cells in the posterior eye, which ultimately leads to blindness. Thus, clinical treatment paradigms for glaucoma are focused on reducing IOP. Normotensive IOPs are established by balancing the production of aqueous fluid from the ciliary body with drainage through the TM to Schlemm's canal. When IOP becomes elevated, TM cells coordinate a homeostatic response to lower IOP, which requires effective and efficient cellular communication. Tunneling nanotubes (TNTs) are transient specialized structures that allow cells to communicate with one another. Actin-rich tubes allow direct transmission of signals and cargoes between cells. This is important to overcome limitations of diffusion-based signaling in aqueous environments such as the anterior eye. Here, we describe a live-cell imaging method for monitoring TNTs in primary TM cells.

Complications after Gonioscopy-Assisted Transluminal Trabeculotomy in glaucoma treatment - literature review.

Glaucoma is a disease that leads to optic nerve damage and irreversible loss of the visual field. Gonioscopy-assisted transluminal trabeculotomy (GATT) is a minimally invasive glaucoma surgery technique, where the surgeon opens the trabecular network and Schlemm's canal to improve the outflow of the aqueous humor. This method has shown efficacy in reducing intraocular pressure in patients with primary and secondary glaucoma. GATT has gained popularity due to its minimally invasive nature, compatibility with cataract surgery and relatively low cost. Despite its advantages, the procedure can be associated with many complications such as hyphema, intraocular pressure spikes and corneal edema. In rare cases, it can lead to Descemet's membrane detachment or cystoid macular edema. The success of GATT procedure mostly depends on the surgeon's skill and experience, but also on the patient's risk factors, including age and preoperative intraocular pressure levels. Further studies are required to understand long outcomes and identify the patients, who may be at higher risk of complications.

Transcriptomic profiling of Schlemm’s canal cells reveals a lymphatic-biased identity and three major cell states

Schlemm’s canal (SC) is central in intraocular pressure regulation but requires much characterization. It has distinct inner and outer walls, each composed of Schlemm’s canal endothelial cells (SECs) with different morphologies and functions. Recent transcriptomic studies of the anterior segment added important knowledge, but were limited in power by SEC numbers or did not focus on SC. To gain a more comprehensive understanding of SC biology, we performed bulk RNA sequencing on C57BL/6 J SC, blood vessel, and lymphatic endothelial cells from limbal tissue (~4,500 SECs). We also analyzed mouse limbal tissues by single-cell and single-nucleus RNA sequencing (C57BL/6 J and 129/Sj strains), successfully sequencing 903 individual SECs. Together, these datasets confirm that SC has molecular characteristics of both blood and lymphatic endothelia with a lymphatic phenotype predominating. SECs are enriched in pathways that regulate cell-cell junction formation pointing to the importance of junctions in determining SC fluid permeability. Importantly, and for the first time, our analyses characterize three molecular classes of SECs, molecularly distinguishing inner wall from outer wall SECs and discovering two inner wall cell states that likely result from local environmental differences. Further, and based on ligand and receptor expression patterns, we document key interactions between SECs and cells of the adjacent trabecular meshwork (TM) drainage tissue. Also, we present cell type expression for a collection of human glaucoma genes. These data provide a new molecular foundation that will enable the functional dissection of key homeostatic processes mediated by SECs as well as the development of new glaucoma therapeutics.

Transcriptomic profiling of Schlemm's canal cells reveals a lymphatic-biased identity and three major cell states.

Schlemm's canal (SC) is central in intraocular pressure regulation but requires much characterization. It has distinct inner and outer walls, each composed of Schlemm's canal endothelial cells (SECs) with different morphologies and functions. Recent transcriptomic studies of the anterior segment added important knowledge, but were limited in power by SEC numbers or did not focus on SC. To gain a more comprehensive understanding of SC biology, we performed bulk RNA sequencing on C57BL/6 J SC, blood vessel, and lymphatic endothelial cells from limbal tissue (~4,500 SECs). We also analyzed mouse limbal tissues by single-cell and single-nucleus RNA sequencing (C57BL/6 J and 129/Sj strains), successfully sequencing 903 individual SECs. Together, these datasets confirm that SC has molecular characteristics of both blood and lymphatic endothelia with a lymphatic phenotype predominating. SECs are enriched in pathways that regulate cell-cell junction formation pointing to the importance of junctions in determining SC fluid permeability. Importantly, and for the first time, our analyses characterize three molecular classes of SECs, molecularly distinguishing inner wall from outer wall SECs and discovering two inner wall cell states that likely result from local environmental differences. Further, and based on ligand and receptor expression patterns, we document key interactions between SECs and cells of the adjacent trabecular meshwork (TM) drainage tissue. Also, we present cell type expression for a collection of human glaucoma genes. These data provide a new molecular foundation that will enable the functional dissection of key homeostatic processes mediated by SECs as well as the development of new glaucoma therapeutics.

Long-term efficacy and safety of ab externo canaloplasty in the Polish Caucasian population with open-angle glaucoma: A 3-year retrospective study.

This study aimed to assess the effectiveness and safety of ab externo canaloplasty over a 3-year follow-up period in Polish Caucasian patients with glaucoma. This retrospective study of a cases series was conducted at the Department of Ophthalmology Medical University of Bialystok, Poland. Primary outcome measures were intraocular pressure and medication burden. Secondary outcome measures were best corrected visual acuity, retinal nerve fiber layer thickness, visual field test results, endothelial cell density, intraoperative and postoperative complications, and additional glaucoma surgery. The study group consisted of 160 eyes diagnosed with early to-moderate primary open-angle glaucoma and treated with ab externo canaloplasty from 2014 to 2020. The criteria for qualified and complete success were intraocular pressure < 18 mmHg or ≥ 20% reduction in intraocular pressure from baseline with or without antiglaucoma medications, respectively. After surgery, the mean intraocular pressure decreased from 19.23 ± 4.33 to 14.52 ± 3.79 mmHg, which constituted a 36.7 ± 7.8% reduction compared to the baseline value. The number of medications decreased by two at the end of the study period (from 2.69 ± 1.05 to 0.32 ± 0.75). Complete and qualified success were achieved in 58.7% and 68.7% of the patients, respectively, at the end of follow-up. An incomplete cannulation of Schlemm's canal was the most common intraoperative complication, occurring in 32 eyes (20%). The most frequent postoperative complications were hyphema, Descemet's membrane detachment, and a transient increase in intraocular pressure. Additional surgical procedure was required in seven cases (4.4%). In 16 patients (10%), medical treatment was re-administered. Overall, our findings suggest that ab externo canaloplasty is a good option for Polish Caucasian patients with primary open-angle glaucoma. It reduces intraocular pressure and has a low postoperative complication rate. Additional glaucoma surgery or re-administration of medications is required if the target intraocular pressure is unsatisfactory.

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.

Schlemm's canal-selective Tie2/TEK knockdown induces sustained ocular hypertension in adult mice

Deficient Angiopoietin-Tie2 signaling is linked to ocular hypertension in glaucoma. Receptor Tie2/TEK expression and signaling at Schlemm's canal (SC) is indispensable for canal integrity and homeostatic regulation of aqueous humor outflow (AHO) and intraocular pressure (IOP), as validated by conditional deletion of Tie2, its ligands (Angpt1, Angpt2 and Angpt3/4) or regulators (Tie1 and PTPRB/VE-PTP). However, these Tie2/TEK knockouts and conditional knockouts are global or endothelial, preventing separation of systemic and ocular vascular defects that impact retinal or renal integrity. To develop a more targeted model of ocular hypertension induced by selective knockdown of Tie2/TEK expressed in SC, we combined the use of viral vectors to target the canal, and two distinct gene-editing strategies to disrupt the Tie2 gene. Adeno-associated virus (AAV2) is known to transduce rodent SC when delivered into the anterior chamber by intracameral injection. First, delivery of Cre recombinase via AAV2.Cre into R26tdTomato/+ reporter mice confirmed preferential and stable transduction in SC endothelium. Next, to disrupt Tie2 expression in SC, we injected AAV2.Cre into homozygous floxed Tie2 (Tie2FL/FL) mice. This led to attenuated Tie2 protein expression along the SC inner wall, decreased SC area and reduced trabecular meshwork (TM) cellularity. Functionally, IOP was significantly and steadily elevated, whereas AHO facility was reduced. In contrast, hemizygous Tie2FL/+ mice responded to AAV2.Cre with inconsistent and low IOP elevation, corroborating the dose-dependency of ocular hypertension on Tie2 expression/activation. In a second model using CRISPR/SaCas9 genome editing, wild-type C57BL/6 J mice injected with AAV2.saCas9-sgTie2 showed similar selective SC transduction and comparable IOP elevation in course and magnitude to that induced by AAV2.Cre in Tie2FL/FL mice. Together, our findings, demonstrate that selective Tie2 knockdown in SC is a targeted strategy that reliably induces chronic ocular hypertension and reproduces glaucomatous damage to the conventional outflow pathway, providing novel models of SC-Tie2 signaling loss valuable for preclinical studies.

Glaucoma-Protective Human Single-Nucleotide Polymorphism in the Angpt2 Locus Increased ANGPT2 Expression and Schlemm Canal Area in Mice-Brief Report.

The ANGPT (angiopoietin)-TEK (tyrosine kinase, endothelial) vascular signaling pathway plays a key role in the formation of Schlemm canal, and loss-of-function mutations in the TEK or ANGPT1 gene are associated with primary congenital glaucoma in children. In genome-wide association studies, an association was identified between protection from primary open-angle glaucoma and the single-nucleotide polymorphism rs76020419 (G>T), located within a predicted miR-145-binding site in the 3' untranslated region of ANGPT2. To date, the functional impact of this variant in the anterior chamber of the eye remains largely unexplored. MT (mutant) mice harboring an orthologous rs76020419 minor allele (T) were generated using CRISPR/Cas9 (clustered regularly interspaced short palindromic repeats/clustered regularly interspaced short palindromic repeat-associated 9). Plasma and tissue samples, including eyes, were collected, and ANGPT2 expression was quantified using ELISA. Anterior segments from eyes were collected from WT (wild-type) and MT mice, and Schlemm canal area was quantified. In the MT group, higher ANGPT2 concentrations were observed in the plasma, lungs, kidneys, and eyes (P=0.0212, P<0.001, P=0.0815, and P=0.0215, respectively). Additionally, the Schlemm canal was larger in MT mice compared with WT mice (P=0.0430). The rs76020419 minor allele (T) is associated with increased levels of ANGPT2 and a larger Schlemm canal in mice. These findings suggest a potential protective mechanism in glaucoma.

Analysis of Schlemm's Canal Measurement and Evaluation with Fourier-Domain Optical Coherence Tomography in Primary Open-Angle Glaucoma

The most common cause of permanent vision loss or blindness in the world is glaucoma. Primary Open Angle Glaucoma (POAG) develops when the eye drainage canals clog over time, increasing intraocular pressure and damaging the optic nerve. In POAG, an ophthalmology examination usually shows an open anterior chamber and chronic, irreversible multifactorial optic neuropathy followed by central visual field loss. OCT is specifically employed to investigate the elasticity of tissue, particularly in Schlemm's canal. This study aims to analyzed the morphological parameters of Schlemm's canal among patients with POAG and normal healthy control. In this observational study, we included one hundred patients, among them 50 patients had POAG, and 50 healthy controls, and both eyes were assessed. We measured the study cohort's and the healthy cohort's eyes' elevated IOP and the Schlemm's canal cross-sectional area (CSA). RT-Vue OCT was used to analyze both eyes' temporal, superior, inferior, and nasal regions. The data were analyzed using both univariate and bivariate methods. The characteristics of the morphological measurement of Schlemm's canal results were similar to those of Kagemann et al. There was a significant difference between age and SC measurement, but no correlation was observed between SC measurement and IOP or visual acuity. OCT is a useful way to evaluate the morphological status of Schlemm Canal in glaucoma patients. The eyes with POAG had smaller Schlemm's Canal- CSA than the normal eyes. The Schlemm canal-CSA in Chinese people had no differences from that of peoples of other races.

Preliminary antifibrotic and vasoconstrictor effects of adrenaline in Schlemm's canal and suprachoroidal minimally invasive glaucoma surgery in primary open-angle glaucoma.

To investigate the antifibrotic and vasoconstrictor effects of adrenaline in Schlemm's canal and suprachoroidal minimally invasive glaucoma surgery (MIGS). Human trabecular meshwork (TM) cells were treated with different concentrations of adrenaline (0%, 0.0005%, 0.01%), and we measured the effects on contractility, cell viability and the expression of key cell cycle and fibrosis genes. Adrenaline 0.05% was also injected intracamerally in five primary open-angle glaucoma patients undergoing iStent inject or MINIject surgery combined with phacoemulsification. All patients were assessed for ocular and systemic adverse reactions, including the effects on intraoperative pupil size, preoperative and postoperative visual acuity, intraocular pressure, and anterior segment OCT results. Adrenaline significantly reduced the contractility of TM cells in a dose-dependent manner (87.8%, 80.6%, 7.9% matrix contraction with adrenaline 0%, 0.0005%, 0.01%, respectively). Adrenaline did not exhibit any significant cytotoxicity even at high concentrations (P > 0.05). Adrenaline 0.01% significantly downregulated the expression of key cell cycle genes in the G2 and M phases, and also decreased the expression of MRTFB and ACTA2 genes (P < 0.05). Intracameral injections of adrenaline 0.05% in the five MIGS patients did not result in any ocular or systemic adverse effects. We recommend intracameral injections of adrenaline 0.05% as a cheap and safe drug to be used before MIGS insertion. Adrenaline decreases the risk of bleeding from the trabecular meshwork and also exhibits antifibrotic effects by arresting the cell cycle, thereby increasing the postoperative success rates in MIGS. What is known Fibrosis is the main cause of surgical failure in minimally invasive glaucoma surgery (MIGS). Mitomycin-C and 5-fluorouracil are too toxic to be used inside the eye. What is new Adrenaline reduced the contractility of trabecular meshwork cells and inhibited the expression of key cell cycle genes and fibrosis genes, without significant cytotoxicity. Intracameral injection of adrenaline 0.05% did not result in any ocular or systemic adverse reactions in MIGS patients.

Robotic Visible-Light Optical Coherence Tomography Visualizes Segmental Schlemm's Canal Anatomy and Segmental Pilocarpine Response.

To use robotic visible-light OCT (vis-OCT) to study circumferential segmental Schlemm's canal (SC) anatomy in mice after topical pilocarpine administration. Anterior segment imaging was performed using a vis-OCT sample arm attached to a 6-degree-of-freedom robotic arm to maintain normal (perpendicular) laser illumination aimed at SC around the limbus. Sixteen mice were studied for repeatability testing and to study aqueous humor outflow (AHO) pathway response to topical drug. Pharmaceutical-grade pilocarpine (1%; n = 5) or control artificial tears (n = 9) were given, and vis-OCT imaging was performed before and 15 minutes after drug application. After SC segmentation, SC areas and volumes were measured circumferentially in control- and drug-treated eyes. Circumferential vis-OCT provided high-resolution imaging of the anterior segment and AHO pathways, including SC. Segmental SC anatomy was visualized with the average cross-sectional area greatest temporal (3971 ± 328 µm 2 ) and the least nasal (2727 ± 218 µm 2 ; p = 0.018). After pilocarpine administration, the iris became flatter, and SC became larger (pilocarpine: 26.8 ± 5.0% vs. control: 8.9 ± 4.6% volume increase; p = 0.030). However, the pilocarpine alteration was segmental as well, with a greater increase observed superior (pilocarpine: 31.6 ± 8.9% vs. control: 1.8 ± 5.7% volume increase; p = 0.023) and nasal (pilocarpine: 41.1 ± 15.3% vs. control: 13.9 ± 4.5% volume increase; p = 0.045). High-resolution circumferential non-invasive imaging using AS-OCT of AHO pathways is possible in living animals with robotic control. Segmental SC anatomy was seen at baseline and was consistent with the known segmental nature of trabecular AHO. Segmental SC anatomical response to a muscarinic agonist was seen as well. Segmental glaucoma drug response around the circumference of AHO pathways is a novel observation that may explain the variable patient response to glaucoma treatments.

Visualization of the Postoperative Position of the Hydrus® Microstent Using Automatic 360° Gonioscopy.

Introduction: Glaucoma, one leading cause of irreversible vision loss worldwide, is primarily caused by elevated intraocular pressure (IOP). Recently, minimally invasive glaucoma surgeries (MIGSs) have become popular due to their shorter surgical times, tissue-sparing nature, and faster recovery. One such MIGS, the Hydrus® nickel-titanium alloy Microstent, helps lower IOP by improving aqueous humor outflow. The NIDEK GS-1 automated 360° gonioscope provides advanced imaging of the chamber angle for evaluation and documentation. The aim of this study was to test automated 360° gonioscopy for the detection of postoperative positional variations after Hydrus® Microstent implantation. This study is the largest to date to evaluate post-op positioning of the Hydrus® Microstent using the NIDEK GS-1. Materials and Methods: This study analyzed postoperative outcomes and stent location in eyes diagnosed with mild to moderate glaucoma that underwent Hydrus® Microstent implantation with or without phacoemulsification. Patients with prior IOP-lowering surgery or vitrectomy were excluded. Analyses of the postoperative Hydrus® Microstent position were based on the evaluation of automated 360° gonioscopy images. Results: Twenty-three eyes were included in the study, and all showed a reduction in IOP and a decrease in antiglaucomatous drop use postoperatively. Postoperative gonoscopic images showed variations in implant position. In all cases, the proximal inlet was clearly visible in the anterior chamber. The degree of protrusion into the anterior chamber was variable. The distal tip of the stent was visible behind the trabecular meshwork in Schlemm's canal in five cases, in the anterior chamber in one case, and not visible in seven cases. In no case did postoperative alterations in the position of the implant lead to explantation. Conclusions: This study demonstrated that the Hydrus® Microstent can effectively lower IOP even in the presence of postoperative positional variations. Automated 360° gonioscopy was found to be a useful tool to verify and document the postoperative position of the implant. Positional changes did not require device explantation in any of the cases evaluated.

In Vivo Assessment of the Pediatric Trabecular Meshwork, Schlemm Canal, and Iridocorneal Angle Using Overhead-Mounted Optical Coherence Tomography

PurposeTo describe the in vivo morphologic characteristics of the trabecular meshwork (TM), Schlemm canal (SC), and iridocorneal angle in pediatric patients with normal eyes, glaucoma and cataract. DesignProspective cohort study Study population70 eyes (41 children) were enrolled. 28 normal eyes, 19 eyes with glaucoma, and 26 eyes with cataract (15 pre-, 11 post-lensectomy). Average age was 2.8±3.0 years at imaging. MethodsPediatric patients undergoing clinically indicated examination under anesthesia underwent overhead-mounted optical coherence tomography (OCT) imaging of the outflow pathway. Images were then evaluated for abnormalities in the outflow pathway. Main outcome measurePresence of thickened TM, SC patency, any iridocorneal angle malformation, and episcleral vessel patency in normal eyes vs. all other eyes. ResultsThickened TM tissue was found in no normal eyes, 47.4% of eyes with glaucoma, and 53.8% of eyes with cataracts. A patent SC was demonstrated in all normal eyes, 32% with glaucoma, and 65.4% with cataracts. Iridocorneal angle abnormality was identified in no normal eyes, 94.7% with glaucoma, and 69.2% with cataracts. Prevalence of iridocorneal angle abnormality was similar in cataract eyes pre- and post-lensectomy. All but one eye with glaucoma secondary to anterior segment dysgenesis had patent episcleral vessels. Intraocular pressure (IOP) at imaging was lower in eyes with than without a patent SC (13.9±3.8mmHg vs. 28.2±11.7mmHg, p<0.001). IOP was lower in eyes with normal iridocorneal angles compared to those with angle malformation (13.9±3.2mmHg vs. 22.6±12.1mmHg, p<0.001). There was no significant difference in IOP between eyes with normal TM thickness compared to those with thickened TM (17.4±8.2mmHg vs.17.4±9.5mmHg, p = 0.943). ConclusionEyes of children with glaucoma demonstrated thickened TM, decreased patency of SC, and abnormalities of the iridocorneal angle on OCT imaging, compared to normal controls. These abnormal findings also appear in many pediatric eyes with cataracts, even prior to lensectomy. Future study is warranted to evaluate the role these structural differences may play in the development of glaucoma following cataract surgery and the significant variation in how individual glaucoma eyes respond to angle surgery.

Historical and Contemporary Debates in Schlemm's Canal-Based MIGS.

Glaucoma is one of the primary causes of blindness worldwide. Canal opening surgery, a type of minimally invasive glaucoma surgery (MIGS) applied in cases of mild to moderate glaucoma, has gained increasing popularity in recent years due to its efficacy in reducing the intraocular pressure, its safety profile, the simplicity of its technique, and the reduced likelihood of compromised vision. Nevertheless, the existing body of histopathological studies remains insufficient for a comprehensive understanding of post-surgical wound healing. Consequently, debates persist among researchers regarding the mechanism through which Schlemm's canal opening surgery reduces the intraocular pressure, as well as the surgical techniques that may impact the outcomes and the factors influencing surgical success. As the history of MIGS is relatively short and lacks sufficient systemic reviews or meta-analyses evaluating the influence of individual factors, this review was conducted to illuminate the disparities in researchers' opinions at the current stage of research.

Modified viscotrabeculotomy versus modified trabeculotomy in late-onset primary congenital, juvenile, and secondary open-angle glaucoma.

To compare modified viscotrabeculotomy (VCO-Tbo) to modified trabeculotomy (Tbo) in late-onset primary congenital, juvenile open-angle, steroid-induced, and pigmentary glaucoma. Patients were randomly assigned to VCO-Tbo and Tbo groups in this study. Intraocular pressure (IOP), antiglaucoma medications, and success/failure rates were assessed. A linear mixed model was used to compare the change trend at different follow-up times. Survival time was evaluated using the Kaplan-Meier graph and Log-Rank test. The mean IOP at 1, 3, and 12 months in the VCO-Tbo group was 14.1 ± 3.1, 15.9 ± 3 and 17 ± 3.1 mmHg, respectively. The mean IOP at the same time points in the Tbo group was 15.9 ± 3.3, 17.6 ± 3.5 and 18.4 ± 3.2 mmHg (P = 0.051, 0.058, 0.088, respectively). The VCO-Tbo group had significantly lower IOP after six months (16.5 ± 4.1 mmHg vs. 18.7 ± 3.8 mmHg; p = 0.031) and by the last visit (16.8 ± 2.1 mmHg vs. 18.8 ± 2 mmHg; p = 0.013). The reduction in the number of medications was significant in both groups compared to baseline (P < 0.001), but there was no significant difference between groups (P = 0.450). The complete and qualified success rate was 43.9% and 34.1% in the VCO-Tbo group and 46.8% and 10.6% in the Tbo group at the final follow-up (p = 0.040, and 0.039, respectively). Both procedures are effective in IOP and medication reduction. The survival time and efficacy of modified trabeculotomy can be augmented by injecting cohesive viscoelastic in the Schlemm's canal.

Transcriptomic profiling of Schlemm's canal cells reveals a lymphatic-biased identity and three major cell states.

Schlemm's canal (SC) is central in intraocular pressure regulation but requires much characterization. It has distinct inner and outer walls, each composed of Schlemm's canal endothelial cells (SECs) with different morphologies and functions. Recent transcriptomic studies of the anterior segment added important knowledge, but were limited in power by SEC numbers or did not focus on SC. To gain a more comprehensive understanding of SC biology, we performed bulk RNA sequencing on C57BL/6J SC, blood vessel, and lymphatic endothelial cells from limbal tissue (~4500 SECs). We also analyzed mouse limbal tissues by single-cell and single-nucleus RNA sequencing (C57BL/6J and 129/Sj strains), successfully sequencing 903 individual SECs. Together, these datasets confirm that SC has molecular characteristics of both blood and lymphatic endothelia with a lymphatic phenotype predominating. SECs are enriched in pathways that regulate cell-cell junction formation pointing to the importance of junctions in determining SC fluid permeability. Importantly, and for the first time, our analyses characterize 3 molecular classes of SECs, molecularly distinguishing inner wall from outer wall SECs and discovering two inner wall cell states that likely result from local environmental differences. Further, and based on ligand and receptor expression patterns, we document key interactions between SECs and cells of the adjacent trabecular meshwork (TM) drainage tissue. Also, we present cell type expression for a collection of human glaucoma genes. These data provide a new molecular foundation that will enable the functional dissection of key homeostatic processes mediated by SECs as well as the development of new glaucoma therapeutics.

Combined Micro-Invasive Glaucoma Surgery (MIGS) with Phacoemulsification in Open Angle Glaucoma: A Systematic Review and Meta-Analysis

The purpose of this study is to compare efficacies and safeties of combined phacoemulsification-Micro-Invasive Glaucoma Surgeries (MIGS) to phacoemulsification only in eyes with open angle glaucoma. Systematic Review and Meta-Analysis. A multi-database literature search was conducted to caputre MIGS articles published prior to April 19th, 2024. Key exclusion criteria were inadequate follow-up, significant loss to follow-up, standalone MIGS surgery, or primary outcomes unreported. MIGS were grouped according to mechanisms of action: 1) Trabecular Meshwork (TM) bypass which improve aqueous drainage into Schlemm's canal (SC), 2) non-GATT Goniotomies which remove TM with varying devices, and 3) GATT which remove TM with a catheter or suture placed into SC. Efficacy was measured by reductions in IOP and medications while safety was compared using incidence of sight-threatening and other adverse events. A total of 95 studies were included, accounting for 9733 eyes followed up at 1-year. The control group had a baseline IOP of 16.9(95%CI 15.9-17.9) mmHg on 1.43(1.19-1.68) medications and a postoperative IOP of 15.2(14.4-15.9) mmHg on 0.80(0.54-1.00) medications. The TM bypass baseline IOP was 18.2(17.6-18.7) mmHg on 1.89(1.78-2.01) medications which lowered to an IOP of 14.8(14.5-15.1) mmHg on 0.80(0.65-0.95) medications at 1-year-postoperation. The non-GATT goniotomy baseline IOP was 20.0(19.2-20.8) mmHg on 2.30(2.09-2.53) medications, and at 1-year followup the IOP was 14.6(14.3-15.0) mmHg on 1.41(1.22-1.62) medications. Lastly, the GATT baseline IOP of 21.8(19.5-24.1) mmHg on 2.90(2.36-3.44) medications was reduced to an IOP of 12.5(10.0-15.0) mmHg on 0.73(0.37-1.09) medications at 1-year-postoperation. All MIGS groups had equal or lower rates of sight-threatening events and secondary glaucoma surgery when compared to control. GATT had the highest hyphema rate at 27.7(13.5-44.5) % followed by non-GATT goniotomy with 15.5(7.8-25.0) %. These were both significantly higher than TM bypass and control groups, with hyphema rates of 3.5(1.6-5.9) % and 4% (only 1 study reporting hyphema rate), respectively. Based on current peer-reviewed articles, there is strong evidence that when compared to phacoemulsification alone, combined phaco-MIGS is beneficial for patients with open angle glaucoma and does not increase the incidence of vision-threatening events. Key limitations of our review stem from heterogeneities in protocol design or outcome reporting, and a limited number of high-quality studies with long-term follow-up.

Refractive Outcomes Following Combined Cataract and Microinvasive Glaucoma Surgery

To compare refractive outcomes in eyes undergoing cataract extraction (CE) alone, CE with goniotomy (CE/goniotomy), and CE with Schlemm's canal stent (CE/SCS) insertion. Retrospective cohort study. Eyes from the Bascom Palmer Glaucoma Repository undergoing CE/goniotomy, CE/SCS insertion, or uncomplicated CE alone between July 2014 and February 2022 were identified. Refraction data were analyzed at post-operative month (POM) 1 and 6 with Kruskal-Wallis and Dunn's tests. Anisometropia was defined as a spherical equivalent (SE) difference of ≥2D. The primary outcome was mean refraction at POM1 and POM6 across the three surgical groups. Secondary outcomes were comparisons of refraction and visual acuity among different goniotomy and SCS devices, as well as incidence of anisometropia. A total of 8,360 eyes (150 CE/goniotomy, 395 CE/SCS, and 7,815 CE alone) from 6,059 patients were analyzed. At POM1, mean SE in the CE/goniotomy, CE/SCS, and CE alone groups was -0.36±0.91D, -0.31±0.85D, and -0.39±0.88D respectively (p=0.019). Mean logMAR VA was 0.10±0.20, 0.08±0.19, and 0.14±0.26 respectively (p=0.002, CE/SCS vs. CE alone). No statistically significant differences were noted at POM6. Anisometropia occurred at POM1 in 2 patients (13.3%) in the CE/goniotomy-CE group, 1 patient (3.2%) in the CE/SCS-CE group, and 184 patients (4.9%) in the CE-CE group (p=0.217). At POM6, mean SEs were -0.38±0.97D (CE/goniotomy), -0.35±0.81D (CE/SCS), and -0.40±0.91D (CE alone; p=0.473). No significant differences in overall refractive outcomes were observed with different SCS or goniotomy devices. Among primary open-angle glaucoma (POAG) / normal-tension glaucoma (NTG) eyes, mean SE at POM1 was -0.36±0.73D (CE/goniotomy), -0.24±0.84D (CE/SCS), and -0.45±0.81D (CE alone; p<0.001). Concurrent SCS insertion or goniotomy with CE was associated with some statistically significant differences in postoperative refraction and visual acuity, although these small magnitude differences were unlikely to be clinically meaningful.