OBJECTIVE: The conventional aqueous outflow pathway, which includes the trabecular meshwork (TM), juxtacanalicular tissue (JCT), and the inner wall endothelium of Schlemm\'s canal (SC), regulates intraocular pressure (IOP) by controlling the aqueous humor outflow resistance. Despite its importance, our understanding of the biomechanics and hydrodynamics within this region remains limited. Fluid-structure interaction (FSI) offers a way to estimate the biomechanical properties of the JCT and SC under various loading and boundary conditions, providing valuable insights that are beyond the reach of current imaging techniques.
METHODS: In this study, a normal human eye was fixed at a pressure of 7 mm Hg, and two radial wedges of the TM tissues, which included the SC inner wall basement membrane and JCT, were dissected, processed, and imaged using 3D serial block-face scanning electron microscopy (SBF-SEM). Four different sets of images were used to create 3D finite element (FE) models of the JCT and inner wall endothelial cells of SC with their basement membrane. The outer JCT portion was carefully removed as the outflow resistance is not in that region, leaving only the SCE inner wall and a few µm of the tissue, which does contain the resistance. An inverse iterative FE algorithm was then utilized to calculate the unloaded geometry of the JCT/SC complex at an aqueous humor pressure of 0 mm Hg. Then in the model, the intertrabecular spaces, pores, and giant vacuole contents were replaced by aqueous humor, and FSI was employed to pressurize the JCT/SC complex from 0 to 15 mm Hg.
RESULTS: In the JCT/SC complex, the shear stress of the aqueous humor is not evenly distributed. Areas proximal to the inner wall of SC experience larger stresses, reaching up to 10 Pa, while those closer to the JCT undergo lower stresses, approximately 4 Pa. Within this complex, giant vacuoles with or without I-pore behave differently. Those without I-pores experience a more significant strain, around 14%, compared to those with I-pores, where the strain is roughly 9%.
CONCLUSIONS: The distribution of aqueous humor wall shear stress is not uniform within the JCT/SC complex, which may contribute to our understanding of the underlying selective mechanisms in the pathway.

The aqueous humor actively interacts with the trabecular meshwork (TM), juxtacanalicular tissue (JCT), and Schlemm\'s canal (SC) through a dynamic fluid-structure interaction (FSI) coupling. Despite the fact that intraocular pressure (IOP) undergoes significant fluctuations, our understanding of the hyperviscoelastic biomechanical properties of the aqueous outflow tissues is limited. In this study, a quadrant of the anterior segment from a normal human donor eye was dynamically pressurized in the SC lumen, and imaged using a customized optical coherence tomography (OCT). The TM/JCT/SC complex finite element (FE) with embedded collagen fibrils was reconstructed based on the segmented boundary nodes in the OCT images. The hyperviscoelastic mechanical properties of the outflow tissues\' extracellular matrix with embedded viscoelastic collagen fibrils were calculated using an inverse FE-optimization method. Thereafter, the 3D microstructural FE model of the TM, with adjacent JCT and SC inner wall, from the same donor eye was constructed using optical coherence microscopy and subjected to a flow load-boundary from the SC lumen. The resultant deformation/strain in the outflow tissues was calculated using the FSI method, and compared to the digital volume correlation (DVC) data. TM showed larger shear modulus (0.92 MPa) compared to the JCT (0.47 MPa) and SC inner wall (0.85 MPa). Shear modulus (viscoelastic) was larger in the SC inner wall (97.65 MPa) compared to the TM (84.38 MPa) and JCT (56.30 MPa). The conventional aqueous outflow pathway is subjected to a rate-dependent IOP load-boundary with large fluctuations. This necessitates addressing the biomechanics of the outflow tissues using hyperviscoelastic material-model. STATEMENT OF SIGNIFICANCE: While the human conventional aqueous outflow pathway is subjected to a large-deformation and time-dependent IOP load-boundary, we are not aware of any studies that have calculated the hyperviscoelastic mechanical properties of the outflow tissues with embedded viscoelastic collagen fibrils. A quadrant of the anterior segment of a normal humor donor eye was dynamically pressurized from the SC lumen with relatively large fluctuations. The TM/JCT/SC complex were OCT imaged and the mechanical properties of the tissues with embedded collagen fibrils were calculated using the inverse FE-optimization algorithm. The resultant displacement/strain in the FSI outflow model was validated versus the DVC data. The proposed experimental-computational workflow may significantly contribute to understanding of the effects of different drugs on the biomechanics of the conventional aqueous outflow pathway.

Provide outcomes up to 12 months postsurgically for sequential canaloplasty and trabeculotomy with the OMNI surgical system (Sight Sciences, Inc) in pseudophakic patients with mild to moderate open-angle glaucoma.
Retrospective, multicenter, single-arm study conducted at 10 multi-subspecialty ophthalmology practices and surgery centers located in 7 states (Arkansas, California, Kansas, Louisiana, Missouri, New York, and Texas).
Eligible patients were pseudophakic, with mild/moderate open-angle glaucoma, 12-month follow-up, and medicated intraocular pressure (IOP) ≤36 mmHg on ≤4 medications preoperatively. One eye per patient was enrolled.
Institutional Review Board approved. All available cases meeting eligibility criteria were enrolled. Analysis of secondary end points was stratified by baseline (BL) IOP (>18 mmHg in group 1 and ≤18 mmHg in group 2) recognizing that treatment goals differed depending on BL IOP.
Primary success was defined as the proportion of patients with ≥20% reduction in IOP from BL or IOP between 6 and 18 mmHg (inclusive) and on the same or fewer medications without secondary surgical intervention (SSI). Other effectiveness end points included mean IOP and number of medications at 12 months. Safety end points were best-corrected visual acuity (BCVA), adverse events (AEs), and SSIs.
Forty-eight patients were enrolled, 24 in each group. Primary success was met by 73%. Mean IOP was reduced in group 1 (21.8 to 15.6 mmHg, P < 0.0001) and remained controlled in group 2 (15.4 to 13.9 mmHg, P = 0.24). Medications went from 1.7 ± 1.3 to 1.2 ± 1.3 (P = 0.024) in group 1 and from 2.0 ± 1.3 to 1.3 ± 1.3 (P = 0.003) in group 2. Adverse events were typical for the patient population undergoing angle surgery. Those reasonably related to the procedure were mild inflammation (13%), IOP spikes (6%), hyphema, corneal edema, and BCVA loss (all 4%). Five patients (10%) required an SSI.
The sequential combination of canaloplasty followed by trabeculotomy performed as stand-alone procedures using the OMNI system in pseudophakic patients with open-angle glaucoma provides effective IOP reduction or sustained IOP control and meaningful medication reduction for up to 12 months postoperatively.

OBJECTIVE: To measure the Schlemm\'s canal (SC) in vivo by Fourier-domain optical coherence tomography (FD-OCT) in a Caucasian paediatric population.
METHODS: Participants of this cross-sectional study were 290 healthy children. In the right eye of each child, SC cross-sectional diameter and area measurements were made with the FD-OCT instrument RTVue® (Optovue Inc, Fremont, CA, USA) in the nasal and temporal quadrants. These SC variables were then assessed for correlation with the factors age, gender, refractive error, anterior chamber angle and trabecular meshwork (TM) metrics. Finally, the reproducibility of the SC measurements was assessed in 30 of the participants.
RESULTS: Mean participant age was 10.7 ± 3.4 years (range 3-18). SC diameters could be measured in both quadrants in 70.6% and 70.4% of subjects, respectively. Mean SC diameters were similar (p = 0.125) for the temporal and nasal quadrants: 266.7 ± 84.1 μm (range 131-509) and 273.2 ± 77.3 μm (range 124-486), respectively. Mean SC areas were also similar (p = 0.167) for the two quadrants: 9975 ± 3514 μm2 (range 4000-23 000) versus 9688 ± 3297 μm2 (range 3000-24 000). No differences were detected in SC measurements according to gender, refractive error or angle and TM measurements (R ≤ 0.116; p ≥ 0.125). The exception was age which was directly correlated with SC size (p ≤ 0.041). The reproducibility of the SC measurements was excellent (intraclass correlation coefficients ≥0.936).
CONCLUSIONS: FD-OCT allows the identification of the SC in children. Our data indicate an increase in SC size produced with age.

OBJECTIVE: To study the effect of implantation of a 5/0 prolene suture segment inside Schlemm\'s canal as an adjunct to deep sclerectomy.
METHODS: This was a prospective, interventional case series of nine eyes of six patients with open angle glaucoma. Patients underwent deep sclerectomy with insertion of a segment of 5/0 prolene into Schlemm\'s canal at the filtration site without suturing. The main outcome measures were: Intraocular pressure (IOP), postoperative interventions, and complications. Ultrasound biomicroscopy of the filtration area as well as the prolene suture was performed at 6 months postoperatively.
RESULTS: Patients were followed for a mean of 8.1 ± 4.5 months. Mean IOP decreased statistically significant from 19 ± 4.2 mmHg preoperatively to 12 mmHg at 15 months postoperatively (P < 0.0001). The number of glaucoma medications was reduced from 3.7 ± 0.7 preoperatively to 0 postoperatively. No postoperative complications were noted. IOP remained in the low teens in all patients out to the last postoperative visit. Yttrium-aluminum-garnet laser goniopuncture was not required in any case.
CONCLUSIONS: Implantation of a 5/0 prolene suture in Schlemm\'s canal during deep sclerectomy was a safe, cost-effective adjunct to maintain the patency of the intrascleral space and Schlemm\'s canal thus controlling IOP for 6 months postoperatively.

Glaucoma is a disease that damages the optic nerve, frequently leading to blindness. Elevated intraocular pressure (IOP) is the only modifiable risk factor for glaucoma, which is expected to affect 80 million people by 2020, causing bilateral blindness in over 10 million individuals. Because pathological changes to Schlemm\'s canal (SC) may account for significant resistance to outflow, there is considerable interest in characterizing and evaluating the Schlemm\'s canal as a target for glaucoma therapeutics. In conventional, two-dimensional culture, human Schlemm\'s canal (HSC) cells lose spatial, mechanical and biochemical cues, resulting in altered gene expression and cell signaling than observed in vivo, compromising the clinical relevance of data obtained from such systems. Here, we report, for the first time, that 3D culture of HSC cells on microfabricated scaffolds with defined physical and biochemical cues, rescued expression of key HSC markers, VE-cadherin and PECAM1, and mediated pore formation, crucial for the Schlemm\'s canal regulation of IOP. We demonstrated that following treatment with the glaucopathogenic agent, TGF-β2, HSC cells undergo an endothelial-mesenchymal transition, which together with the increase in extracellular matrix (ECM) proteins might account for the decrease in outflow facility observed in patients with high TGF-β2 levels in their aqueous humor. We also demonstrated that unlike 2D cultures, 3D cultures of HSC cells are amenable to gene transfer. Thus, our data imply that 3D culture of HSC cells may be used as a platform to advance our understanding of HSC physiology and pathology and as a model for high-throughput drug and gene screening.