Long-term outcomes of canaloplasty and phaco-canaloplasty in the treatment of open angle glaucoma: a single-surgeon experience.

PURPOSE: To evaluate and compare the long-term outcomes of canaloplasty and phaco-canaloplasty in the treatment of open angle glaucoma and assess the prognostic factors associated with surgical outcome. METHODS: A 48-month retrospective analysis was performed on n = 133 open angle glaucoma eyes treated with canaloplasty and n = 57 open angle glaucoma eyes treated with phaco-canaloplasty by a single surgeon. Surgical success was defined according to six criteria, achieving a target intraocular pressure (IOP) ≤ 21, 18 or 15 mmHg on glaucoma medications (qualified success) or without any further treatment (complete success), including laser therapy or surgery. Kaplan-Meier survival analysis and Cox regression analysis were performed to evaluate surgical success and preoperative factors associated with surgical outcome. Surgical complications in the early postoperative period were compared between canaloplasty and phaco-canaloplasty. RESULTS: Canaloplasty and phaco-canaloplasty significantly reduced postoperative IOP and number of glaucoma medications (p = 0.001 for both). Phaco-canaloplasty showed higher rates of cumulative surgical success over canaloplasty, but only for target IOP ≤ 21 and ≤ 18 (p = 0.018 and p = 0.011, respectively). A preoperative number of > 4 glaucoma medications predicted surgical failure. Phaco-canaloplasty was associated with a higher rate of IOP peaks in the first month compared with canaloplasty (40.4% vs 12.7%, p = 0.000). CONCLUSION: Canaloplasty and phaco-canaloplasty demonstrated long-term efficacy in the treatment of open angle glaucoma, with phaco-canaloplasty showing higher rates of surgical success compared to canaloplasty, but not for target IOPs lower than 16 mmHg. Patients on more than 4 preoperative glaucoma medications may not be good candidates for canaloplasty and may benefit from other surgical options.

Genome-wide RNA sequencing of ocular fibroblasts from glaucomatous and normal eyes: Implications for glaucoma management.

Primary open angle glaucoma is a leading cause of visual impairment and blindness which is commonly treated with drugs or laser but may require surgery. Tenon's ocular fibroblasts are involved in wound-healing after glaucoma filtration surgery and may compromise a favourable outcome of glaucoma surgery by contributing to fibrosis. To investigate changes in gene expression and key pathways contributing to the glaucomatous state we performed genome-wide RNA sequencing. Human Tenon's ocular fibroblasts were cultured from normal and glaucomatous human donors undergoing eye surgery (n = 12). mRNA was extracted and RNA-Seq performed on the Illumina platform. Differentially expressed genes were identified using a bioinformatics pipeline consisting of FastQC, STAR, FeatureCounts and edgeR. Changes in biological functions and pathways were determined using Enrichr and clustered using Cytoscape. A total of 5817 genes were differentially expressed between Tenon's ocular fibroblasts from normal versus glaucomatous eyes. Enrichment analysis showed 787 significantly different biological functions and pathways which were clustered into 176 clusters. Tenon's ocular fibroblasts from glaucomatous eyes showed signs of fibrosis with fibroblast to myofibroblast transdifferentiation and associated changes in mitochondrial fission, remodeling of the extracellular matrix, proliferation, unfolded protein response, inflammation and apoptosis which may relate to the pathogenesis of glaucoma or the detrimental effects of topical glaucoma therapies. Altered gene expression in glaucomatous Tenon's ocular fibroblasts may contribute to an unfavourable outcome of glaucoma filtration surgery. This work presents a genome-wide transcriptome of glaucomatous versus normal Tenon's ocular fibroblasts which may identify genes or pathways of therapeutic value to improve surgical outcomes.

Intraoperative challenges and outcomes of pediatric cataract surgery following glaucoma filtering surgery.

PURPOSE: To analyze the intraoperative challenges of cataract surgery in children, following glaucoma filtering surgery. METHODS: This was a retrospective study to analyze intra-op challenges and outcomes of pediatric cataract surgery in post-glaucoma filtration surgery eyes, between January 2007 and December 2019. RESULTS: We included 20 eyes of 16 children. The most common glaucoma surgery performed was trabeculectomy and trabeculotomy (14 eyes). The median age at the time of cataract surgery was 74.5 months. The most common cataract surgery performed was lens aspiration with posterior chamber intraocular lens implantation (LA + PCIOL) (9/20). The most common intraoperative challenge faced was difficulty in capsulorrhexis (ten eyes), followed by extension of primary posterior capsulotomy (six eyes). At the final follow up eight eyes had improvement in visual acuity, five eyes had stable visual acuity and five eyes had a drop in visual acuity. In 12/20 eyes IOL was implanted, nine eyes in-the-bag and three eyes had in ciliary sulcus. None of the IOLs in the bag had decentration of IOL. The median postoperative IOP (p = 0.12) and median number of postoperative AGM (p = 0.13) at 2 years remained stable compared to the preoperative values. The IOP remained well controlled in 4 eyes without anti-glaucoma medications and in 14 eyes with anti-glaucoma medications and none needed additional surgery for IOP control. Two eyes developed retinal detachment postoperatively. CONCLUSION: Cataract surgery in pediatric eyes with prior glaucoma surgeries, have challenges with capsulorrhexis and IOL stability. The visual outcomes were reasonably good so was the IOP control.

MiR-146a reduces fibrosis after glaucoma filtration surgery in rats.

PURPOSE: To explore the impact of microRNA 146a (miR-146a) and the underlying mechanisms in profibrotic changes following glaucoma filtering surgery (GFS) in rats and stimulation by transforming growth factor (TGF)-ß1 in rat Tenon's capsule fibroblasts. METHODS: Cultured rat Tenon's capsule fibroblasts were treated with TGF-ß1 and analyzed with microarrays for mRNA profiling to validate miR-146a as the target. The Tenon's capsule fibroblasts were then respectively treated with lentivirus-mediated transfection of miR-146a mimic or inhibitor following TGF-ß1 stimulation in vitro, while GFS was performed in rat eyes with respective intraoperative administration of miR-146a, mitomycin C (MMC), or 5-fluorouracil (5-FU) in vivo. Profibrotic genes expression levels (fibronectin, collagen Iα, NF-KB, IL-1ß, TNF-α, SMAD4, and α-smooth muscle actin) were determined through qPCR, Western blotting, immunofluorescence staining and/or histochemical analysis in vitro and in vivo. SMAD4 targeting siRNA was further used to treat the fibroblasts in combination with miR-146a intervention to confirm its role in underlying mechanisms. RESULTS: Upregulation of miR-146a reduced the proliferation rate and profibrotic changes of rat Tenon's capsule fibroblasts induced by TGF-ß1 in vitro, and mitigated subconjunctival fibrosis to extend filtering blebs survival after GFS in vivo, where miR-146a decreased expression levels of NF-KB-SMAD4-related genes, such as fibronectin, collagen Iα, NF-KB, IL-1ß, TNF-α, SMAD4, and α-smooth muscle actin(α-SMA). Additionally, SMAD4 is a key target gene in the process of miR-146a inhibiting fibrosis. CONCLUSIONS: MiR-146a effectively reduced TGF-ß1-induced fibrosis in rat Tenon's capsule fibroblasts in vitro and in vivo, potentially through the NF-KB-SMAD4 signaling pathway. MiR-146a shows promise as a novel therapeutic target for preventing fibrosis and improving the success rate of GFS.

[Clinical characteristics and surgical management outcomes of glaucoma secondary to congenital ectropion uveae: a preliminary analysis of penetrating Schlemm's canaloplasty].

Objective: To investigate the clinical characteristics and treatment outcomes of glaucoma secondary to congenital ectropion uveae (CEU) using penetrating Schlemm's canaloplasty. Methods: This was a retrospective case series study. Medical records of patients diagnosed with glaucoma secondary to CEU and undergoing penetrating Schlemm's canaloplasty at the Eye Hospital of Wenzhou Medical University between August 2020 and December 2021 were collected. Clinical characteristics including the extent and location of iris ectropion, type of glaucoma, were analyzed. Follow-up visits were conducted at 1, 3, 6 months, and 1 year postoperatively. Visual acuity, intraocular pressure (IOP), anterior segment and fundus condition, filtering bleb morphology, use of IOP-lowering medications, ultrasound biomicroscopy results, and other indicators were analyzed to summarize surgical outcomes. Results: Six cases (6 eyes) of glaucoma secondary to CEU were included, all unilateral, with 3 left eyes and 3 right eyes; median age was 10.0 (5.3, 28.8) years; including 3 males and 3 females. Preoperative IOP was (31.7±10.0) mmHg (1 mmHg=0.133 kPa), and the preoperative number of IOP-lowering medications used was 2.0 (2.0, 3.2). The extent of iris ectropion in the 6 cases ranged from 270 ° to 360 °, with peripheral anterior synechiae corresponding to the location of iris ectropion, and angle closure with the degree of synechiae extending beyond Schwalbe's line. No surgical complications occurred in any of the 6 cases postoperatively. At 1 month postoperatively, the IOP was (16.4±3.2) mmHg, with a median of 0.0 (0.0, 1.5) medications used. At 3 months postoperatively, the IOP was (14.8±6.0) mmHg, with a median of 0.0 (0.0, 2.2) medications used. At 6 months postoperatively, the IOP was (18.1±6.1) mmHg, with a median of 0.0 (0.0, 0.5) medications used. Among them, 5 patients had a follow-up period of 1 year postoperatively, all achieving controlled IOP without the use of IOP-lowering medications, with an average IOP of (15.5±3.1) mmHg. No obvious filtering bleb formation was observed at the surgical site in all patients. Conclusions: Glaucoma secondary to CEU manifests primarily as closed-angle glaucoma, with a correspondence between the closure range of anterior iris adhesions in the angle and the extent of iris ectropion. Penetrating Schlemm's canaloplasty demonstrates favorable and stable efficacy for its treatment.

[Glaucoma Filtration Surgery - Bleb-forming Procedures]. / Filtrierende Glaukomchirurgie ­ Verfahren mit Bildung eines Filterkissens.

Glaucoma filtration surgery has been a standard surgical therapy for decades. An increasing knowledge about wound healing processes in the eye, the introduction of antimetabolite treatment and continuous improvements of the surgical technique helped making trabeculectomy - the prototype filtration surgery - a very effective therapeutic tool. However, best results will only be regularly achieved with a high level of experience and time dedicated to postoperative follow-up. Furthermore, the potential for severe early and late complications still remains high. Thus, novel stent-based filtration surgery approaches, such as the Preserflo and the XEN shunt have been introduced. This review presents these three bleb-forming filtration procedures, covering the basic principles of surgical technique, data on effectivity as well as complications.

New suture probe canaloplasty combined with suprachoroidal collagen implantation.

PURPOSE: To present the modified surgery technique of new suture probe canaloplasty with a specially prepared monofilament 4.0 polypropylene suture combined with suprachoroidal drainage (ScD) and collagen sheet implantation for non-penetrating glaucoma surgery. METHODS: Prospective study with a twelve months follow-up. A standard 4/0 polypropylene suture (ProleneTM by Ethicon; thickness: approximately 250 m) is cut and shaped with an ophthalmic knife (MANI® Crescent Knife, Mani Inc 8-3 Kiyohara Industrial Park, Utsunomiya, Tochigi 321-3231, Japan) to create a blunt end without sharp or compressed edges. This improves suture probe canaloplasty by providing a more stable and smoother probing device. Schlemm's canal is prepared using the standard technique of canaloplasty with suprachoroidal drainage. Then, instead of using the canaloplasty microcatheter or the previously published 6/0 double-helix suture, Schlemm's canal is probed with the blunt ending of the 4/0 Prolene suture. After successful 360-degree probing, a doubled 10/0 polypropylene tension suture is threaded through the tip of the 4/0 suture. The 4/0 suture is then pulled back and the 10/0 tension sutures are tied at both ends to tension Schlemm's canal. A special collagen sheet (Ologen®) is placed in suprachoroidal space, and the scleral flap is firmly sewed. RESULTS: 115 eyes were included in this prospective study. In 113 cases the Schlemm's canal could completely be probed with the suture probe and canaloplasty with ScD and collagen sheet implantation succeeded. In two cases the intervention was transformed to 360-degree suture trabeculotomy due to an intraoperative cheese-wiring. Twelve months after successful new suture probe canaloplasty with ScD and Collagen Implantation the IOP had decreased by 37.1% (from 21.6 ± 6.0 mmHg with 3.3 different IOP lowering eye drops to 13.5 ± 3.5 mmHg with 1.0 eye drops). 16 Patients did not achieve sufficient IOP levels and underwent 360-degree suture trabeculotomy during the follow-up. One patient had to be treated with further glaucoma surgery to achieve a sufficient IOP level. Complications were hyphema, postoperative IOP elevation and transient hypotony. No serious or sight-threatening complications occurred. CONCLUSION: New suture probe canaloplasty with ScD and collagen sheet implantation yields the opportunity to conduct a cost-effective canaloplasty easier and less complicated than with the previously described method with the twisted 6/0 suture. The safety profile and IOP lowering effect is comparable. In cases where complete probing fails, there is still the opportunity to switch to suture trabeculotomy over the majorly probed part of Schlemm's canal. The pressure lowering effect of the deep sclerectomy with ScD and suprachoroidal collagen sheet implant seems to have an additional impact on the sufficient pressure lowering procedure.

Using a Novel, Subconjunctival, Sustained-Release Mitomycin C Formulation in a Rabbit Model of Filtration Surgery with Gel Stent Implantation.

Purpose: To investigate gel stent implantation with and without intraoperative sustained-release mitomycin C (MMC SR) in a rabbit model for gel stent implantation, and to examine aqueous humor outflow (AHO) postimplantation. Methods: Four groups of rabbits were included. Group 1 was untreated (control). Groups 2, 3, and 4 received the gel stent without MMC, with MMC solution (subconjunctival injection), and with MMC SR (subconjunctival injection), respectively. Intraocular pressure (IOP) and AHO were assessed via tonometry and indocyanine green-based angiography, respectively. The main efficacy measure was change in IOP from baseline. Results: Following gel stent implantation, Groups 2, 3, and 4 maintained ≥20% IOP reduction (response) for a median duration of 1 week, 6.5 weeks, and 30 weeks, respectively. Angiography showed normal aqueous humor drainage (Group 1) beginning at the perilimbal trabecular plexus and continuing posteriorly to episcleral outflow vessels. Following implantation, drainage occurred preferentially and directly into the subconjunctival bleb. Conclusions: Gel stent implantation with MMC SR was most effective in achieving sustained, long-term IOP reduction in the rabbit model, compared with implantation with or without MMC solution. Bleb presence and the postimplantation aqueous angiography results indicated redirection of the AHO to the subconjunctival vasculature and presumed lymphatics, suggesting efficient glaucoma filtration to lower IOP in this model. This rabbit model and aqueous angiography may help refine understanding of the mechanism of action of minimally invasive glaucoma surgeries and ultimately translate to improved surgical devices and procedures for patients with glaucoma.

Successful resolution of serous macular detachment following glaucoma-filtering surgery alone for acquired optic disc pit maculopathy.

PURPOSE: To describe a case of acquired glaucomatous optic disc pit-related maculopathy successfully treated with glaucoma filtering surgery alone. CASE DESCRIPTION: A 67-year-old male was diagnosed with advanced primary open angle glaucoma in both eyes, with a cup: disc ratio of 0.85 in the right eye and 0.95 in the left eye. Visual acuity at presentation was 20/60, and intraocular pressure was 14 mm Hg in the left eye. The fundus of the left eye revealed a serous macular retinal detachment due to an acquired optic disc pit. RESULTS: The left eye of the patient underwent combined cataract and glaucoma filtering surgery. The serous macular detachment resolved completely 15 months after surgery, with a documented visual acuity of 20/40 and intraocular pressure of 10 mm Hg without the use of additional antiglaucoma medications. There was no recurrence of serous macular detachment even after the two-year follow-up visit. CONCLUSION: This case demonstrates that controlling intraocular pressure alone resulted in complete resolution of serous macular detachment in acquired optic disc pit maculopathy without the need for pars plana vitrectomy.

Bleb vessel density as a predictive factor for surgical revisions after Preserflo Microshunt implantation.

PURPOSE: Bleb failure is a common complication after glaucoma filtration surgery. Different bleb classification schemes incorporating filtration bleb vascularization have been proposed, but the reported correlation with intraocular pressure (IOP) has been variable, possibly because of subjective vascularization grading. The purpose of the present study was to evaluate bleb vascularization after Preserflo Microshunt (PM) implantation using anterior segment OCT-angiography (AS-OCTA) as a biomarker for bleb failure. METHODS: Twenty-three eyes of twenty-three patients underwent PM implantation. Up to 12 months after surgery PM scleral passage-centred AS-OCTA measurements (PLEX Elite 9000) for bleb-vessel density (BVD) determination were performed and IOP as well as necessity for surgical revisions (needling and open revision) were documented. After multi-step image analysis (region of interest definition, artefact removal, binarization, BVD calculation), the predictive value of early postoperative BVD for surgical revisions was assessed using logistic regression modelling. RESULTS: Baseline IOP (23.57 ± 7.75 mmHg) decreased significantly to 8.30 ± 2.12, 9.17 ± 2.33 and 11.70 ± 4.40 mmHg after 1, 2 and 4 week(s), and 13.48 ± 5.83, 11.87 ± 4.49, 12.30 ± 6.65, 11.87 ± 3.11 and 13.05 ± 4.12 mmHg after 2, 3, 6, 9 and 12 month(s), respectively (p < 0.001). Nine patients (39%) needed surgical revisions after a median time of 2 months. Bleb vessel densities at 2 and 4 weeks were significantly associated with future surgical revisions upon logistic regression analysis (2 W/4 W likelihood-ratio test p-value: 0.0244/0.0098; 2 W/4 W area under the receiver operating characteristics curve: 0.796/0.909). CONCLUSION: Filtration bleb vessel density can be determined using AS-OCTA in the early postoperative period and is predictive for bleb failure after PM implantation.

A MEK inhibitor arrests the cell cycle of human conjunctival fibroblasts and improves the outcome of glaucoma filtration surgery.

Better agents are needed to improve glaucoma filtration surgery outcomes compared to current ones. The purpose of this study is to determine whether mitogen-activated protein kinase kinase (MEK) inhibitors can effectively arrest the cell cycle of human conjunctival fibroblasts (HCFs) and inhibit the formation of fibrosis and scarring following glaucoma filtration surgery. A cell counting kit­8 assay revealed that the MEK inhibitor PD0325901 exhibited concentration-dependent growth inhibition of HCFs. Quantitative PCR, immunocytochemistry, and western blotting demonstrated decreased expression of proliferating cell nuclear antigen (PCNA) and cyclin D1 and increased expression of p27 in HCFs treated with PD0325901. Flow cytometry indicated that PD0325901 arrested the cell cycle of HCFs in the G0/1 phase. The cell-migration assay showed that HCF migration rate was significantly suppressed by PD0325901 exposure. Rabbits were divided into PD0325901-treatment and control groups, and glaucoma filtration surgery was performed. Although intraocular pressure did not differ between PD0325901-treatment and control groups, bleb height was greater in the treatment group. Histopathological evaluation revealed that fibrotic changes were significantly attenuated in the PD0325901-treatment group compared to the control group. In conclusion, the MEK inhibitor impedes HCF proliferation via cell-cycle arrest and may be beneficial for glaucoma filtration surgery by reducing bleb scarring.

Outcomes of Filtering Surgery Versus Clear Lens Extraction in Young Patients With Angle-Closure Glaucoma.

PURPOSE: To compare the effect of filtering surgery versus clear lens extraction in young patients with medically uncontrolled angle-closure glaucoma (ACG). DESIGN: Retrospective, nonrandomized, comparative, interventional study. METHODS: We reviewed the medical charts of patients with the following scenarios: (1) age ≤40 years; (2) diagnosis of ACG without cataract, including primary angle-closure glaucoma (PACG), nanophthalmic ACG, and ACG combined with retinal dystrophies; and (3) ACG undergoing filtering surgery or clear lens extraction. The main outcomes including intraocular pressure (IOP), number of medications, best-corrected visual acuity, and severe complications were extracted at the postoperative early (within 1 week) and late stage (>3 months) follow-up. RESULTS: Data from 160 eyes of 130 young patients with ACG were available. Eyes with 76 PACG, 12 nanophthalmic ACG, and 26 ACG with retinal diseases underwent filtering surgery, whereas eyes with 22 PACG, 12 nanophthalmic ACG, and 12 ACG with retinal diseases received clear lens extraction. Overall, filtering surgery and clear lens extraction resulted in significant but comparable IOP and drug reductions at the postoperative late stage in each ACG subgroup, with similar complete success rates between 2 treatments (all P > .05). Regarding the safety, filtering surgery and patients with retinal diseases were independent factors associated with postoperative malignant glaucoma (P < .05 in both multivariable logistic regression models). CONCLUSIONS: This study highlights that the efficacy of clear lens extraction is comparable to that of filtering surgery in medically uncontrolled ACG in young patients, but clear lens extraction is safer, especially for young patients with ACG comorbid with retinal diseases.

Clinical Characteristics and Surgical Outcomes of Turkish Patients With Pediatric Glaucoma Who Underwent Glaucoma Surgery in a University Hospital.

PURPOSE: To describe the clinical characteristics and outcomes of a pediatric cohort surgically treated for primary or secondary pediatric glaucoma (PPG/SPG). METHODS: A retrospective chart review was conducted of all patients with pediatric glaucoma who had surgery between 2013 and 2021. Relevant demographic and clinical data were cumulated and analyzed. RESULTS: Forty-two eyes of 29 patients (18 girls and 11 boys) were included: 22 (52.4%) primary congenital glaucoma (PCG), 7 (16.7%) juvenile open-angle glaucoma, and 13 (30.9%) SPG. Mean ages at presentation were 2.57 ± 2.87, 131.96 ± 27.71, and 62.09 ± 65.12 months, respectively. In this study, eyes with PCG presented the earliest, with the highest intraocular pressure (IOP) and thickest central corneal thickness (CCT). The mean number of glaucoma surgeries was 1.48 ± 0.71, with 38.1% of the eyes needing two or more glaucoma surgeries; trabeculectomy was the most frequent glaucoma surgery in this cohort. After surgical intervention, the overall mean IOP dropped from 32.25 ± 12.97 to 18.10 ± 9.23 mm Hg (P < .001). Moreover, the percentage using antiglaucoma medications decreased from 100% to 35.7% at the final visit, as did the number of medications prescribed per eye (2.69 ± 0.92 vs 1.05 ± 1.46, P ≤ .001). Mean best corrected visual acuity (BCVA), in patients who could have their BCVA measured, improved from 0.61 ± 0.61 to 0.53 ± 0.51 logMAR at final follow-up. CONCLUSIONS: Surgical intervention was shown to provide a well-controlled IOP, decrease dependance on glaucoma medications, and improve BCVA in both PPG and SPG. Multiple surgical interventions may be necessary in the treatment of some pediatric patients with glaucoma. Prognostically, thicker CCT was significantly associated with worse IOP control, more glaucoma surgeries, and more antiglaucoma medications at the final visit. Initial BCVA correlated significantly with BCVA at the final visit. [J Pediatr Ophthalmol Strabismus. 2024;61(3):188-197.].

Incidence of glaucoma filtration surgery from disease onset of open-angle glaucoma.

AIMS: To investigate the rate and risk factors of undergoing glaucoma filtration surgery (GFS) in patients with newly diagnosed open-angle glaucoma (OAG). METHODS: This is a population-based historic cohort study, consisting of 9420 patients older than 45 years diagnosed with OAG during 1997-2010. Follow-up spanned from 1997 to 2017. We obtained data for trabeculectomy (TRE), deep sclerectomy (DS), and glaucoma drainage implant (GDI) surgeries from national administrative healthcare registers by hospital billing data. We plotted the cumulative incidence of GFS and carried out a multivariate Poisson regression analysis adjusted for age, sex, hospital district, systemic comorbidities, and the number of IOP-lowering drugs. We reported incidence rate ratios (IRR) with 95% confidence intervals (CI) for GFS after the onset of OAG. RESULTS: The cumulative incidence of GFS at 5 years from OAG onset was 3.1% and at 10 years 5.4%. Age over 80 years at baseline was associated with lower GFS incidence (IRR 0.51, CI 0.31-0.84). The number of IOP-lowering drugs in the first 2 years of treatment correlated with the risk of GFS increasing from (IRR 3.23, CI 2.32-4.50) for two drugs, (IRR 7.44, CI 5.28-10.47) for three and to (IRR 14.95, CI 10.38-21.52) for four drugs. CONCLUSION: This study characterized the treatment path of OAG from diagnosis to surgical intervention refining the role of GFS among glaucoma therapies.

Minimally Invasive Glaucoma Surgery: Latest Developments and Future Challenges.

The development of minimally invasive glaucoma surgeries (MIGSs) was intended to provide safe and modestly efficacious modalities for early intervention of mild-to-moderate glaucoma, with minimal trauma and rapid recovery. They were mainly ab interno procedures that reduce intraocular pressure by facilitating the aqueous outflow by bypassing the trabecular meshwork resistance, reinforcing the uveoscleral flow via the supraciliary space, and reducing aqueous production by the ciliary body. While the cumulating evidence helps shape the role of the available MIGS, the exponential new development and advancement in this field has expanded the territory of MIGS. Apart from developing subconjunctival MIGS filtration devices (Xen gel stent and PRESERFLO MicroShunt), there is a tendency to revisit the "traditional" MIGS for alternative use and to modify the procedures with consideration of the fundamental aqueous outflow physiology. Combined MIGS has also been suggested, based on the theory that their different mechanisms may provide additive or synergistic effects. The advancement of laser procedures is also promising and could supplement unmet needs along the glaucoma treatment algorithm. This review examines the broad array of MIGS, updates the recent findings, discusses their potential alternative applications, and explores future challenges.

MiR-29b Downregulation by p53/Sp1 Complex Plays a Critical Role in Bleb Scar Formation After Glaucoma Filtration Surgery.

Purpose: To investigate the function and mechanism of tumor protein p53 in pathological scarring after glaucoma filtration surgery (GFS) using human Tenon's fibroblasts (HTFs) and a rabbit GFS model. Methods: The expression of p53 in bleb scarring after GFS and transforming growth factor-ß (TGF-ß)-induced HTFs (myofibroblasts [MFs]) was examined by western blot and immunochemical analysis. The interaction between p53 and specificity protein 1 (Sp1) was investigated by immunoprecipitation. The role of p53 and Sp1 in the accumulation of collagen type I alpha 1 chain (COL1A1) and the migration of MFs was evaluated by western blot, quantitative real-time polymerase chain reaction (qRT-PCR), wound healing, and Transwell assay. The regulatory mechanisms among p53/Sp1 and miR-29b were detected via qRT-PCR, western blot, luciferase reporter assay, and chromatin immunoprecipitation assay. The therapeutic effect of mithramycin A, a specific inhibitor of Sp1, on scarring formation was evaluated in a rabbit GFS model. Results: p53 was upregulated in bleb scar tissue and MFs. p53 and Sp1 form a transcription factor complex that induces the accumulation of COL1A1 and promotes the migration of MFs through downregulation of miR-29b, a known suppressor of COL1A1. The p53/Sp1 axis inhibits miR-29b expression by the direct binding promoter of the miR-29b gene. Mithramycin A treatment attenuated bleb scar formation in vivo. Conclusions: The p53/Sp1/miR-29b signaling pathway plays a critical role in bleb scar formation after GFS. This pathway could be targeted for therapeutic intervention of pathological scarring after GFS. Translational Relevance: Our research indicates that inhibition of p53/Sp1/miR-29b is a promising therapeutic strategy for preventing post-GFS pathological scarring.

[Review by the French Glaucoma Society on the roles of new surgical techniques in glaucoma]. / Mise au point de la Société française du glaucome sur la place des nouvelles techniques chirurgicales dans le glaucome.

The surgical management of glaucoma has been enriched in recent years by the arrival of new surgical techniques as a group known as MIGS (minimally invasive glaucoma surgery). The objective of these new techniques is to reduce intraocular pressure (IOP) while limiting the risk of complications of conventional filtering surgery and allowing faster visual recovery. MIGS can be classified into three main categories depending on the route used to promote the outflow of aqueous humor: the trabecular route, the suprachoroidal route and the subconjunctival route. MIGS using the subconjunctival route are also called minimally invasive bleb surgery (MIBS). These new techniques do not replace conventional filtering surgery, which remains the gold standard technique, but now offer new alternatives for the surgical management of glaucoma patients in combination with cataract surgery or as stand-alone procedures.

A machine learning approach to predict the glaucoma filtration surgery outcome.

This study aimed at predicting the filtration surgery (FS) outcome using a machine learning (ML) approach. 102 glaucomatous patients undergoing FS were enrolled and underwent ocular surface clinical tests (OSCTs), determination of surgical site-related biometric parameters (SSPs) and conjunctival vascularization. Break-up-time, Schirmer test I, corneal fluorescein staining, Meibomian gland expressibility; conjunctival hyperemia, upper bulbar conjunctiva area of exposure, limbus to superior eyelid distance; and conjunctival epithelial and stromal (CET, CST) thickness and reflectivity (ECR, SCR) at AS-OCT were considered. Successful FS required a 30% baseline intraocular pressure reduction, with values ≤ 18 mmHg with or without medications. The classification tree (CT) was the ML algorithm used to analyze data. At the twelfth month, FS was successful in 60.8% of cases, whereas failed in 39.2%. At the variable importance ranking, CST and SCR were the predictors with the greater relative importance to the CART tree construction, followed by age. CET and ECR showed less relative importance, whereas OSCTs and SSPs were not important features. Within the CT, CST turned out the most important variable for discriminating success from failure, followed by SCR and age, with cut-off values of 75 µm, 169 on gray scale, and 62 years, respectively. The ROC curve for the classifier showed an AUC of 0.784 (0.692-0.860). In this ML approach, CT analysis found that conjunctival stroma thickness and reflectivity, along with age, can predict the FS outcome with good accuracy. A pre-operative thick and hyper-reflective stroma, and a younger age increase the risk of FS failure.