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Keywords = schlemm’s canal

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14 pages, 1528 KiB  
Article
Surgical Outcomes of Gonioscopy-Assisted Transluminal Trabeculotomy (GATT) in Primary and Secondary Open- and Closed-Angle Glaucoma
by Liron Naftali Ben Haim, Veronika Yehezkeli, Assaf Kratz, Nimrod Dar, Tal Sharon, Gal Harel, Zvia Burganski-Eliash and Avner Belkin
Diagnostics 2025, 15(10), 1226; https://doi.org/10.3390/diagnostics15101226 - 13 May 2025
Viewed by 586
Abstract
Background: Gonioscopy-assisted transluminal trabeculotomy (GATT) is a minimally invasive, ab interno conjunctival-sparing glaucoma surgery aimed at the trabecular meshwork and the inner wall of Schlemm’s canal. The goal of this study is to report on the success of GATT in a large group [...] Read more.
Background: Gonioscopy-assisted transluminal trabeculotomy (GATT) is a minimally invasive, ab interno conjunctival-sparing glaucoma surgery aimed at the trabecular meshwork and the inner wall of Schlemm’s canal. The goal of this study is to report on the success of GATT in a large group of patients with a wide variety of open- and closed-angle glaucomas with or without cataract extraction and to report on risk factors for failure. Methods: A retrospective chart review of consecutive patients with primary or secondary open- or closed-angle glaucoma who underwent GATT, with or without concomitant phacoemulsification. Demographics, baseline clinical characteristics, and postoperative outcomes were collected from patients’ medical records. Primary outcomes were success rates (IOP of 18 mmHg or lower and one of the following: IOP reduction > 30% from baseline on the same or fewer medications or an IOP ≤ baseline with fewer medications as compared to baseline) and complication rates. Intraocular pressure (IOP) and the number of glaucoma medications were secondary outcome measures. Results: GATT was performed on 126 eyes of 121 patients. Mean follow-up was 583 ± 266 days. Cumulative success at 1Y was 0.88 for GATT combined with cataract extraction, 0.96 for GATT alone, 0.88 for primary open-angle glaucoma (POAG), 0.89 for secondary open-angle glaucoma (SOAG), and 0.76 for primary angle-closure glaucoma (PACG). IOP decreased from a mean of 20.65 mmHg to 14.1 mmHg, and medication decreased from a mean of 3.47 to 1.4 at the last follow-up. Forty-four eyes (34%) were classified as failures. Factors associated with an increased risk of failure were worse preoperative corrected visual acuity (OR = 2.46, p = 0.024) and a postoperative IOP spike (OR = 2.62, p = 0.028). Twelve eyes (9.5%) required further surgery for IOP control. Risk factors for requiring further surgery for IOP control were preoperative maximal IOP (OR = 1.066, p = 0.047) and a postoperative IOP spike (OR = 4.531, p = 0.036). Conclusions: GATT achieved good surgical success with good IOP and medication reduction across a wide range of glaucomas, in combination with lens extraction or as a standalone procedure. GATT should be considered early in the treatment paradigm of medically uncontrolled glaucoma. Full article
(This article belongs to the Special Issue Diagnosis and Management of Ophthalmic Disorders)
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31 pages, 412 KiB  
Review
Visual Function After Schlemm’s Canal-Based MIGS
by Masayuki Kasahara and Nobuyuki Shoji
J. Clin. Med. 2025, 14(7), 2531; https://doi.org/10.3390/jcm14072531 - 7 Apr 2025
Viewed by 926
Abstract
Filtration surgery is highly effective in lowering intraocular pressure; however, it is associated with a higher risk of severe complications. Visual dysfunction may persist in relatively uneventful cases because of induced astigmatism or worsening optical aberrations. Therefore, for early- to moderate-stage glaucoma, an [...] Read more.
Filtration surgery is highly effective in lowering intraocular pressure; however, it is associated with a higher risk of severe complications. Visual dysfunction may persist in relatively uneventful cases because of induced astigmatism or worsening optical aberrations. Therefore, for early- to moderate-stage glaucoma, an increasing number of surgeons are prioritizing surgical safety and preserving postoperative visual function by opting for minimally invasive glaucoma surgery (MIGS). Among the various MIGS techniques, canal-opening surgery—targeting aqueous outflow through the Schlemm’s canal (Schlemm’s canal-based MIGS, CB-MIGS)—has gained increasing popularity. Unlike filtration surgery, CB-MIGS does not require creating an aqueous outflow pathway between the intraocular and extraocular spaces. Consequently, it is considered a minimally invasive procedure with a reduced risk of severe complications and is increasingly being chosen for suitable cases. Although this surgical technique has limitations in lowering intraocular pressure, it avoids the manipulation of the conjunctiva or sclera and is primarily performed through a small corneal incision. Therefore, a minimal impact on induced astigmatism or postoperative refractive changes is expected. However, few reviews comprehensively summarize postoperative changes in visual function. Therefore, this study reviews the literature on visual function after CB-MIGS, focusing on changes in best-corrected visual acuity (BCVA), refraction, astigmatism, and the effectiveness of visual field preservation to assess the extent of these postoperative changes. Hyphema is the primary cause of early postoperative vision loss and is often transient in cases in which other complications would have led to visual impairment. Severe complications that threaten vision are rare. Additionally, compared with filtration surgery, postoperative visual recovery tends to be faster, and the degree of induced astigmatism is comparable to that of standalone cataract surgery. When combined with cataract surgery, the refractive error is at the same level as that of cataract surgery alone. However, in some cases, mild hyperopic shifts may occur because of axial length shortening, depending on the extent of intraocular pressure reduction. This possibility has been highlighted in several studies. Regarding the effectiveness of slowing the progression of visual field defects, most studies have focused on short- to medium-term postoperative outcomes. Many of these studies have reported the sufficient suppression of progression rates. However, studies with large sample sizes and long-term prospective designs are limited. To establish more robust evidence, future research should focus on conducting larger-scale, long-term investigations. Full article
(This article belongs to the Special Issue Clinical Debates in Minimally Invasive Glaucoma Surgery (MIGS))
14 pages, 6544 KiB  
Article
Identification and Validation of Key Biomarkers in the Proximal Aqueous Humor Outflow Pathway
by Rong Du, Enzhi Yang, Madison Clark, Ningli Wang and Yiqin Du
Curr. Issues Mol. Biol. 2025, 47(3), 147; https://doi.org/10.3390/cimb47030147 - 25 Feb 2025
Cited by 1 | Viewed by 764
Abstract
Glaucoma is a leading cause of irreversible blindness, with elevated intraocular pressure (IOP) as the most important risk factor. The trabecular meshwork (TM) and Schlemm’s canal are the main components of the proximal aqueous humor outflow pathway. Their dysfunction is a major contributor [...] Read more.
Glaucoma is a leading cause of irreversible blindness, with elevated intraocular pressure (IOP) as the most important risk factor. The trabecular meshwork (TM) and Schlemm’s canal are the main components of the proximal aqueous humor outflow pathway. Their dysfunction is a major contributor to IOP elevation. This study aims to identify and validate key biomarkers for TM and Schlemm’s canal endothelial (SCE) cells. A Microarray was performed on characterized human TM and SCE cells to analyze their transcriptome profiling. Differentially expressed genes (DEGs) were identified and cross-referenced with published single-cell RNA sequencing (scRNA-Seq) datasets to ensure cell-specific relevance. Further validation was performed using qPCR and re-confirmed on the scRNA-seq datasets. One-way ANOVA was used for statistical analysis, and p < 0.05 was considered significant. The Microarray revealed 341 DEGs, with TM cells enriched in metabolic and signaling pathways and SCE cells enriched in adhesion, immune, and morphogenesis-related processes. Cross-referencing with scRNA-Seq data refined the list of candidate biomarkers, and qPCR confirmed the significant gene expression differences between TM and SCE cells. CTTNBP2 and MGARP were identified as TM cell markers. JAM2, PODXL, and IFI27 are new SCE cell biomarkers. The validated biomarkers offer insights into glaucoma pathophysiology and lay the groundwork for targeted therapies. Full article
(This article belongs to the Section Molecular Medicine)
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10 pages, 2627 KiB  
Article
Diabetes Mellitus: A Risk Factor in Schlemm’s Canal-Based Minimally Invasive Glaucoma Surgery
by Etsuo Chihara, Eri Nakano and Tomoyuki Chihara
J. Clin. Med. 2024, 13(24), 7660; https://doi.org/10.3390/jcm13247660 - 16 Dec 2024
Viewed by 689
Abstract
Objectives: The objective of this study was to evaluate the impact of diabetes mellitus (DM) on the outcome of Schlemm’s canal-based minimally invasive glaucoma surgery (MIGS). Methods: In a retrospective interventional cohort study, postoperative intraocular pressure (IOP) and intracameral bleeding were analyzed [...] Read more.
Objectives: The objective of this study was to evaluate the impact of diabetes mellitus (DM) on the outcome of Schlemm’s canal-based minimally invasive glaucoma surgery (MIGS). Methods: In a retrospective interventional cohort study, postoperative intraocular pressure (IOP) and intracameral bleeding were analyzed in 25 diabetic patients and 84 non-diabetic patients, with primary open-angle glaucoma (POAG) or ocular hypertension (OH). Results: The mean follow-up period for all 109 eyes was 35.3 ± 24.8 months. There was no significant difference in preoperative IOP between cohorts with or without diabetes. However, the post-surgical IOP between 3 months and 2 years was significantly higher in the cohort with diabetes (p = 0.019 to 0.001). The 3-year survival probability of achieving an IOP ≤ 15 mmHg was 17.8 ± 0.09% in patients with diabetes, significantly lower than the 30.4 ± 0.06% observed in patients without diabetes (p = 0.042 Log-rank test). The 3-year survival probability of achieving an IOP ≤ 18 mmHg was 56.7 ± 0.12% in patients with diabetes compared to 79.5 ± 0.05% in patients without diabetes, indicating a marginally significant difference between cohorts with and without diabetes (p = 0.065). When the random effect of diabetes mellitus (DM) was analyzed alongside the fixed effects of preoperative IOP, age, refractive error, and the extent of canal opening using a multivariate linear mixed model, DM emerged as a significant risk factor for higher postoperative IOP at both 6 and 12 months (p < 0.001). Conclusions: Diabetes mellitus is a significant risk factor for poor outcomes following Schlemm’s canal-based MIGS, particularly in achieving lower postoperative IOP. Full article
(This article belongs to the Section Ophthalmology)
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9 pages, 1940 KiB  
Article
One-Year Outcomes of Trabeculotomy with 120°, 180°, or 360° Schlemm’s Canal Incision for Primary Open-Angle Glaucoma: A Retrospective Study
by Hidetsugu Mori, Tatsunori Kiriishi, Masatoshi Omi, Masayuki Ohnaka and Hisanori Imai
J. Clin. Med. 2024, 13(24), 7653; https://doi.org/10.3390/jcm13247653 - 16 Dec 2024
Cited by 1 | Viewed by 681
Abstract
Background/Objectives: Primary open-angle glaucoma (POAG), if caused by elevated intraocular pressure (IOP), may require a trabeculotomy (LOT), in which the trabecular meshwork (TM) and Schlemm’s canal (ISC) are incised. However, the association between the incision angle and outcomes remains unclear. Therefore, in this [...] Read more.
Background/Objectives: Primary open-angle glaucoma (POAG), if caused by elevated intraocular pressure (IOP), may require a trabeculotomy (LOT), in which the trabecular meshwork (TM) and Schlemm’s canal (ISC) are incised. However, the association between the incision angle and outcomes remains unclear. Therefore, in this study, we investigated the surgical outcomes of a trabeculotomy combined with cataract surgery in patients with POAG over a 12-month follow-up period. Methods: We included 66 patients (corresponding to 83 eyes) with POAG who underwent trabeculotomy ab externo with a metal probe (M-LOT: 120° incision of the TM and ISC), ab interno with a Kahook Dual Blade® (K-LOT: 180° incision of the TM and ISC), or ab interno with a 5-0 nylon suture (S-LOT: 360° incision of the TM and ISC) between January 2015 and December 2022. We assessed IOP, the percentage reduction from preoperative IOP, the number of IOP-lowering medications taken, the incidence of postoperative complications, and the success rate using Kaplan–Meier survival analysis. Results: The median IOP was significantly lower than the baseline across all three groups. The number of IOP-lowering medications taken was significantly reduced only in the M-LOT group. The mean percentage reduction from the preoperative IOP in the K-LOT group was significantly lower than that in the M and S-LOT groups. Beween those subjected to an ab ineterno LOT, the S-LOT group demonstrated a significantly higher rate of IOP reduction 12 months after the operation compared to the K-LOT group. Kaplan–Meier cumulative survival analyses revealed a lower success rate for the K-LOT group than for the M and S-LOT groups. The M-LOT group had the lowest incidence of hyphema and IOP spikes, whereas the S-LOT group had the highest incidence of these complications. Conclusions: The M-, K-, and S-LOTs had different surgical outcomes during the 12 months of follow-up, with the M-LOT group showing the fewest complications. These results will help in selecting the most suitable trabeculotomy strategy for patients with POAG. Based on the postoperative outcomes of the ab interno K- and S-LOTs, a wider incision of the TM and ISC leads to effective IOP reduction. Full article
(This article belongs to the Section Ophthalmology)
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12 pages, 1853 KiB  
Article
Visualization of the Postoperative Position of the Hydrus® Microstent Using Automatic 360° Gonioscopy
by Julian Alexander Zimmermann, Sarah Kleemann, Jens Julian Storp, Cedric Weich, Ralph-Laurent Merté, Nicole Eter and Viktoria Constanze Brücher
J. Clin. Med. 2024, 13(17), 5333; https://doi.org/10.3390/jcm13175333 - 9 Sep 2024
Viewed by 1487
Abstract
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 [...] Read more.
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. Full article
(This article belongs to the Special Issue Clinical Debates in Minimally Invasive Glaucoma Surgery (MIGS))
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28 pages, 1580 KiB  
Review
Historical and Contemporary Debates in Schlemm’s Canal-Based MIGS
by Etsuo Chihara and Teruhiko Hamanaka
J. Clin. Med. 2024, 13(16), 4882; https://doi.org/10.3390/jcm13164882 - 19 Aug 2024
Cited by 3 | Viewed by 1508
Abstract
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 [...] Read more.
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. Full article
(This article belongs to the Special Issue Clinical Debates in Minimally Invasive Glaucoma Surgery (MIGS))
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8 pages, 2878 KiB  
Case Report
A Case Report of Secondary Glaucoma in a Patient with HTLV-1: Discussion about the Management of Secondary Glaucoma Due to Recurrent Granulomatous Uveitis
by Kenta Ashikaga, Teruhiko Hamanaka, Mayumi Hosogai, Takao Tanaka, Shintaro Nakao and Toshinari Funaki
J. Clin. Transl. Ophthalmol. 2024, 2(2), 26-33; https://doi.org/10.3390/jcto2020003 - 29 Mar 2024
Viewed by 1306
Abstract
Purpose: to investigate secondary glaucoma resulting from uveitis in a patient infected with Human T-cell Leukemia Virus Type 1 (HTLV-1) pathologically and discuss the management of glaucoma with recurrent uveitis. Clinical course: An octogenarian woman diagnosed as a carrier of HTLV-1 experienced recurrent [...] Read more.
Purpose: to investigate secondary glaucoma resulting from uveitis in a patient infected with Human T-cell Leukemia Virus Type 1 (HTLV-1) pathologically and discuss the management of glaucoma with recurrent uveitis. Clinical course: An octogenarian woman diagnosed as a carrier of HTLV-1 experienced recurrent uveitis and a sudden rise in intraocular pressure (IOP) in both eyes. Due to the uncontrolled IOP and severely damaged visual field in her left eye, a combined procedure of trabeculectomy and DGIS (glaucoma drainage implant surgery, Baerveldt 350) was performed. The presence of HTLV-1 provirus was detected in the aqueous humor. Her trabeculectomy sample was processed for light microscopic observation. Following an irregular follow-up, she presented with a sudden decrease in vision and pain in her fellow eye, four years after the glaucoma surgeries. Her right eye exhibited a significant accumulation of mutton-fat-like keratic precipitates. Results: Clinical manifestations revealed the presence of granulomatous uveitis. The combined glaucoma surgery, along with continuous topical corticosteroid medication post-surgery in her left eye, effectively suppressed the high IOP spikes and the recurrence of uveitis for 4 years. The pathological examination of the outflow pathways showed a range of damages in Schlemm’s canal (SC), including SC endothelial loss, narrowing, and occlusion, as well as loss of trabecular meshwork (TM) cells and fused TM beams. Conclusion: Combined GDIS and trabeculectomy represents a promising approach for managing such refractory cases of secondary glaucoma. Continuous topical corticosteroid medication is strongly recommended to prevent irreversible changes in SC and TM associated with granulomatous uveitis. Full article
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11 pages, 841 KiB  
Article
Anterior Scleral Thickness and Anterior Segment Biometrics Measured with Swept Source Ocular Coherence Tomography in High Myopic Eyes with and without Glaucoma: A Comparative Study
by Bachar Kudsieh, Rocio Vega-González, Sofia Bryan, Elena Almazan-Alonso, Mariluz Puertas, Lucia Gutiérrez-Martin, Ignacio Flores-Moreno, Jorge Ruiz-Medrano, Muhsen Samaan and Jose Maria Ruiz-Moreno
Diagnostics 2024, 14(6), 655; https://doi.org/10.3390/diagnostics14060655 - 20 Mar 2024
Cited by 2 | Viewed by 1735
Abstract
Background: To assess the anterior scleral thickness (AST), Schlemm’s canal diameter (SCD), trabecular meshwork diameter (TMD) and conjunctiva tenon capsule thickness (CTT) in high myopic (HM) subjects and HM subjects with glaucoma (HMG) compared to control eyes. Methods: One hundred and twenty [...] Read more.
Background: To assess the anterior scleral thickness (AST), Schlemm’s canal diameter (SCD), trabecular meshwork diameter (TMD) and conjunctiva tenon capsule thickness (CTT) in high myopic (HM) subjects and HM subjects with glaucoma (HMG) compared to control eyes. Methods: One hundred and twenty eyes were included, and AST at 0, 1, 2 and 3 mm from the scleral spur, SCD, TMD and CTT were measured. Results: Mean age was 64.2 ± 11.0 years, and the temporal SCD and temporal TMD were significantly longer in the HMG subjects compared to the controls (380.0 ± 62 μm vs. 316.7 ± 72 μm, p = 0.001) and (637.6 ± 113 μm vs. 512.1 ± 97 μm, p = 0.000), respectively. There were no significant differences between the HM and HMG subjects in SCD and TMD (all p > 0.025). Compared to the HM subjects, the temporal AST0 (432.5 ± 79 μm vs. 532.8 ± 99 μm, p = 0.000), temporal AST1 (383.9 ± 64 μm vs. 460.5 ± 80 μm, p = 0.000), temporal AST2 (404.0 ± 68 μm vs. 464.0 ± 88 μm, p = 0.006) and temporal AST3 (403.0 ± 80 μm vs. 458.1 ± 91 μm, p = 0.014) were significantly thinner in the HMG group. No differences were found between the CTT in the three groups (all p > 0.025). Conclusions: Our data indicate a thinner AST in HMG subjects and no differences in SCD and TMD between HM and HMG subjects. Full article
(This article belongs to the Special Issue Optical Coherence Tomography (OCT): State of the Art)
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20 pages, 8957 KiB  
Article
Exploring the Ocular Absorption Pathway of Fasudil Hydrochloride towards Developing a Nanoparticulate Formulation with Improved Performance
by Barzan Osi, Ali A. Al-Kinani, Zinah K. Al-Qaysi, Mouhamad Khoder and Raid G. Alany
Pharmaceutics 2024, 16(1), 112; https://doi.org/10.3390/pharmaceutics16010112 - 15 Jan 2024
Cited by 8 | Viewed by 2281
Abstract
Rho-kinase (ROCK) inhibitors represent a new category of anti-glaucoma medications. Among them, Fasudil hydrochloride, a selective ROCK inhibitor, has demonstrated promising outcomes in glaucoma treatment. It works by inhibiting the ROCK pathway, which plays a crucial role in regulating the trabecular meshwork and [...] Read more.
Rho-kinase (ROCK) inhibitors represent a new category of anti-glaucoma medications. Among them, Fasudil hydrochloride, a selective ROCK inhibitor, has demonstrated promising outcomes in glaucoma treatment. It works by inhibiting the ROCK pathway, which plays a crucial role in regulating the trabecular meshwork and canal of Schlemm’s aqueous humor outflow. This study aims to investigate the ocular absorption pathway of Fasudil hydrochloride and, subsequently, develop a nanoparticle-based delivery system for enhanced corneal absorption. Employing the ionic gelation method and statistical experimental design, the factors influencing chitosan nanoparticle (Cs NP) characteristics and performance were explored. Fasudil in vitro release and ex vivo permeation studies were performed, and Cs NP ocular tolerability and cytotoxicity on human lens epithelial cells were evaluated. Permeation studies on excised bovine eyes revealed significantly higher Fasudil permeation through the sclera compared to the cornea (370.0 μg/cm2 vs. 96.8 μg/cm2, respectively). The nanoparticle size (144.0 ± 15.6 nm to 835.9 ± 23.4 nm) and entrapment efficiency range achieved (17.2% to 41.4%) were predominantly influenced by chitosan quantity. Cs NPs showed a substantial improvement in the permeation of Fasudil via the cornea, along with slower release compared to the Fasudil aqueous solution. The results from the Hen’s Egg Test Chorioallantoic Membrane (HET-CAM) and Bovine Corneal Opacity and Permeability (BCOP) tests indicated good conjunctival and corneal biocompatibility of the formulated chitosan nanoparticles, respectively. Lens epithelial cells displayed excellent tolerance to low concentrations of these nanoparticles (>94% cell viability). To the best of our knowledge, this is the first report on the ocular absorption pathway of topically applied Fasudil hydrochloride where the cornea has been identified as a potential barrier that could be overcome using Cs NPs. Full article
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12 pages, 2523 KiB  
Article
Myo/Nog Cells Increase in Response to Elevated Intraocular Pressure and Mitigate Ganglion Cell Death in a Mouse Model of Glaucoma
by Paul Lecker, Karanveer Johal, Alexa McGrath, John Spikes, Jake Bernstein, Victoria MacPherson, Rushil Brahmbhatt, Nada Fadl, Edgar Weyback-Liogier, Sarah Adams, Rachel Souza, E-Jine Tsai, Mark Martin, Jacquelyn Gerhart, Grezgorz Gorski, Federica De Cecco, Brian Heist, Sebastian Egberts, Mindy George-Weinstein and Arturo Bravo-Nuevo
Appl. Sci. 2023, 13(22), 12423; https://doi.org/10.3390/app132212423 - 17 Nov 2023
Cited by 1 | Viewed by 1718
Abstract
Glaucoma is one of the leading causes of blindness worldwide. Decreased aqueous humor drainage causes an increase in intraocular pressure (IOP), which in turn damages the ganglion cells of the retina and optic nerve. A mouse model of glaucoma was used to examine [...] Read more.
Glaucoma is one of the leading causes of blindness worldwide. Decreased aqueous humor drainage causes an increase in intraocular pressure (IOP), which in turn damages the ganglion cells of the retina and optic nerve. A mouse model of glaucoma was used to examine the behavior of Myo/Nog (M/N) cells, which were previously shown to respond to cataract surgery and retinopathy induced by hypoxia, light damage, and intravitreal injection of human retinal pigment epithelial cells. M/N cells express the skeletal-muscle-specific transcription factor MyoD, the bone morphogenetic protein inhibitor Noggin, and brain-specific angiogenesis inhibitor 1 (BAI1). Glaucoma was induced by injecting microbeads into the anterior chamber (AC) of the right eye to obstruct the flow of aqueous humor into the trabecular meshwork. IOP was elevated within three days of addition of microbeads. Loss of retinal ganglion cells (RGCs) and thinning of the ganglion cell layer–nerve fiber layer (GCL-NFL) was observed in tissue sections by day 32. The injection of microbeads resulted in an increase in BAI1-positive (+) M/N cells in the trabecular meshwork, ciliary body, canal of Schlemm, cornea, and ganglion cell layer (GCL). M/N cells ingested microbeads. The effect of further increasing the population of M/N cells on IOP and RGC loss was determined by injecting BAI1+ cells isolated from the brain into the AC of both eyes. Exogenous M/N cells prelabeled with CellTracker™ Red were found in the same tissues as the endogenous population of M/N cells in eyes with and without elevated IOP. The addition of M/N cells did not significantly reduce IOP in bead-injected eyes. However, there were significantly more RGCs and the NFL was thicker in glaucomatous eyes with M/N cell supplementation than eyes injected with phosphate-buffered saline. The numbers of RGCs and NFL thickness were similar in glaucomatous and non-glaucomatous eyes after adding M/N cells. These results demonstrate that endogenous M/N cells respond to elevated IOP in the anterior and posterior segments in response to induction of glaucoma. M/N cells’ mitigation of RGC loss may reflect a neuroprotective effect within the retina, as opposed to a significant drop in IOP. Full article
(This article belongs to the Special Issue Advances in Visual Neuroscience)
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13 pages, 3149 KiB  
Article
Effects of Schlemm’s Canal Suture Implantation Surgery and Pilocarpine Eye Drops on Trabecular Meshwork Pulsatile Motion
by Qing Sang, Rong Du, Chen Xin and Ningli Wang
Biomedicines 2023, 11(11), 2932; https://doi.org/10.3390/biomedicines11112932 - 30 Oct 2023
Cited by 1 | Viewed by 1639
Abstract
The trabecular meshwork is an important structure in the outflow pathway of aqueous humor, and its movement ability directly affects the resistance of aqueous humor outflow, thereby affecting the steady state of intraocular pressure (IOP). (1) Objective: The purpose of this study was [...] Read more.
The trabecular meshwork is an important structure in the outflow pathway of aqueous humor, and its movement ability directly affects the resistance of aqueous humor outflow, thereby affecting the steady state of intraocular pressure (IOP). (1) Objective: The purpose of this study was to preliminarily estimate the effects of pilocarpine eye drops and trabeculotomy tunneling trabeculoplasty (3T) on trabecular meshwork (TM) pulsatile motion via phase-sensitive optical coherence tomography (Phs-OCT). (2) Method: In a prospective single-arm study, we mainly recruited patients with primary open-angle glaucoma who did not have a history of glaucoma surgery, and mainly excluded angle closure glaucoma and other diseases that may cause visual field damage. The maximum velocity (MV) and cumulative displacement (CDisp) of the TM were quantified via Phs-OCT. All subjects underwent Phs-OCT examinations before and after the use of pilocarpine eye drops. Then, all subjects received 3T surgery and examinations of IOP at baseline, 1 day, 1 week, 1 month, 3 months, and 6 months post-surgery. Phaco-OCT examinations were performed at 3 and 6 months post-surgery, and the measurements were compared and analyzed. (3) Results: The MV of TM before and after the use of pilocarpine eye drops was 21.32 ± 2.63 μm/s and 17.00 ± 2.43 μm/s. The CDisp of TM before and after the use of pilocarpine eye drops was 0.204 ± 0.034 μm and 0.184 ± 0.035 μm. After the use of pilocarpine eye drops, both the MV and CDisp significantly decreased compared to those before use (p < 0.001 and 0.013, respectively). The IOP decreased from baseline at 22.16 ± 5.23 mmHg to 15.85 ± 3.71 mmHg after 3 months post-surgery and from 16.33 ± 2.51 mmHg at 6 months post-surgery, showing statistically significant differences (p < 0.001). The use of glaucoma medication decreased from baseline at 3.63 ± 0.65 to 1.17 ± 1.75 at 3 months and 1.00 ± 1.51 at 6 months post-surgery; the differences were statistically significant (p < 0.001). Additionally, there was no statistically significant difference in the MV between 3 and 6 months after surgery compared to baseline (p = 0.404 and 0.139, respectively). Further, there was no statistically significant difference in the CDisp between 3 and 6 months after surgery compared to baseline (p = 0.560 and 0.576, respectively) (4) Conclusions: After the preliminary study, we found that pilocarpine eye drops can attenuate TM pulsatile motion, and that 3T surgery may reduce IOP without affecting the pulsatile motion status of the TM. Full article
(This article belongs to the Section Molecular and Translational Medicine)
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31 pages, 22717 KiB  
Review
Trabecular Meshwork Movement Controls Distal Valves and Chambers: New Glaucoma Medical and Surgical Targets
by Murray Johnstone, Chen Xin, Elizabeth Martin and Ruikang Wang
J. Clin. Med. 2023, 12(20), 6599; https://doi.org/10.3390/jcm12206599 - 18 Oct 2023
Cited by 6 | Viewed by 3263
Abstract
Herein, we provide evidence that human regulation of aqueous outflow is by a pump-conduit system similar to that of the lymphatics. Direct observation documents pulsatile aqueous flow into Schlemm’s canal and from the canal into collector channels, intrascleral channels, aqueous veins, and episcleral [...] Read more.
Herein, we provide evidence that human regulation of aqueous outflow is by a pump-conduit system similar to that of the lymphatics. Direct observation documents pulsatile aqueous flow into Schlemm’s canal and from the canal into collector channels, intrascleral channels, aqueous veins, and episcleral veins. Pulsatile flow in vessels requires a driving force, a chamber with mobile walls and valves. We demonstrate that the trabecular meshwork acts as a deformable, mobile wall of a chamber: Schlemm’s canal. A tight linkage between the driving force of intraocular pressure and meshwork deformation causes tissue responses in milliseconds. The link provides a sensory-motor baroreceptor-like function, providing maintenance of a homeostatic setpoint. The ocular pulse causes meshwork motion oscillations around the setpoint. We document valves entering and exiting the canal using real-time direct observation with a microscope and multiple additional modalities. Our laboratory-based high-resolution SD-OCT platform quantifies valve lumen opening and closing within milliseconds synchronously with meshwork motion; meshwork tissue stiffens, and movement slows in glaucoma tissue. Our novel PhS-OCT system measures nanometer-level motion synchronous with the ocular pulse in human subjects. Movement decreases in glaucoma patients. Our model is robust because it anchors laboratory studies to direct observation of physical reality in humans with glaucoma. Full article
(This article belongs to the Special Issue Advances in Glaucoma Management and Intraocular Pressure Physiology)
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19 pages, 12830 KiB  
Article
Biomechanics of the JCT and SC Inner Wall Endothelial Cells with Their Basement Membrane Using 3D Serial Block-Face Scanning Electron Microscopy
by Alireza Karimi, Reza Razaghi, Mary J. Kelley, Ted S. Acott and Haiyan Gong
Bioengineering 2023, 10(9), 1038; https://doi.org/10.3390/bioengineering10091038 - 4 Sep 2023
Cited by 7 | Viewed by 1958
Abstract
Background: More than ~70% of the aqueous humor exits the eye through the conventional aqueous outflow pathway that is comprised of the trabecular meshwork (TM), juxtacanalicular tissue (JCT), the inner wall endothelium of Schlemm’s canal (SC). The flow resistance in the JCT and [...] Read more.
Background: More than ~70% of the aqueous humor exits the eye through the conventional aqueous outflow pathway that is comprised of the trabecular meshwork (TM), juxtacanalicular tissue (JCT), the inner wall endothelium of Schlemm’s canal (SC). The flow resistance in the JCT and SC inner wall basement membrane is thought to play an important role in the regulation of the intraocular pressure (IOP) in the eye, but current imaging techniques do not provide enough information about the mechanics of these tissues or the aqueous humor in this area. Methods: A normal human eye was perfusion-fixed and a radial wedge of the TM tissue from a high-flow region was dissected. The tissues were then sliced and imaged using serial block-face scanning electron microscopy. Slices from these images were selected and segmented to create a 3D finite element model of the JCT and SC cells with an inner wall basement membrane. The aqueous humor was used to replace the intertrabecular spaces, pores, and giant vacuoles, and fluid–structure interaction was employed to couple the motion of the tissues with the aqueous humor. Results: Higher tensile stresses (0.8-kPa) and strains (25%) were observed in the basement membrane beneath giant vacuoles with open pores. The volumetric average wall shear stress was higher in SC than in JCT/SC. As the aqueous humor approached the inner wall basement membrane of SC, the velocity of the flow decreased, resulting in the formation of small eddies immediately after the flow left the inner wall. Conclusions: Improved modeling of SC and JCT can enhance our understanding of outflow resistance and funneling. Serial block-face scanning electron microscopy with fluid–structure interaction can achieve this, and the observed micro-segmental flow patterns in ex vivo perfused human eyes suggest a hypothetical mechanism. Full article
(This article belongs to the Section Biomechanics and Sports Medicine)
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11 pages, 3207 KiB  
Case Report
Descemet’s Membrane Detachment during Phacocanaloplasty: Case Series and In-Depth Literature Review
by Marta Orejudo de Rivas, Juana Martínez Morales, Elena Pardina Claver, Diana Pérez García, Itziar Pérez Navarro, Francisco J. Ascaso Puyuelo, Julia Aramburu Clavería and Juan Ibáñez Alperte
J. Clin. Med. 2023, 12(17), 5461; https://doi.org/10.3390/jcm12175461 - 23 Aug 2023
Cited by 4 | Viewed by 1496
Abstract
This article presents three cases of Descemet’s membrane detachment (DMD) occurring during ‘ab externo’ phacocanaloplasty procedures in three patients with uncontrolled primary open-angle glaucoma (OAG) and discusses the management of this condition by reviewing the available literature. Following a successful 360° cannulation of [...] Read more.
This article presents three cases of Descemet’s membrane detachment (DMD) occurring during ‘ab externo’ phacocanaloplasty procedures in three patients with uncontrolled primary open-angle glaucoma (OAG) and discusses the management of this condition by reviewing the available literature. Following a successful 360° cannulation of Schlemm’s canal (SC), the microcatheter was withdrawn while an ophthalmic viscosurgical device (OVD) was injected into the canal. During passage through the inferonasal quadrant, a spontaneous separation of the posterior layer of the cornea was observed. Each case was managed differently after diagnosis, with the third case being drained intraoperatively based on experience gained from the previous cases. On the first postoperative day, slit-lamp biomicroscopy (BMC) revealed multiple DMDs in case one and a hyphema in the lower third of a deep anterior chamber. In the other two cases, a single DMD was observed. The second case developed hemorrhagic Descemet membrane detachment (HDMD), while the other two were non-hemorrhagic. In all three cases, anterior segment optical coherence tomography (AS-OCT) revealed the presence of retrocorneal hyperreflective membranes indicative of DMDs. These membranes were located in the periphery of the cornea and did not impact the visual axis. After evaluation, a small incision was made in the inferotemporal DMD of the first case. However, for the two remaining cases, a strategy of watchful waiting was deemed appropriate due to the location and size of the DMDs, as they did not affect the best-corrected visual acuity (BCVA). Over time, the patients demonstrated progressive improvement with a gradual reduction in the size of the DMDs. Full article
(This article belongs to the Special Issue Advances in Glaucoma Surgery)
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