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Purpose To compare outcomes of phaco-canaloplasty (PC) and phaco-non-penetrating deep sclerectomy (PDS) with a viscoelastic compound. Methods This study included 29 eyes after PC and 30 after PDS. Indications were uncontrolled primary open-angle glaucoma (POAG) and a cataract. Corrected distance visual acuity (CDVA), intraocular pressure (IOP), and number of medications were evaluated. Follow-up examinations were performed on days 1 and 7, and after 1, 3, 6, and 12 months. Complete and qualified success was an IOP ≤ 18 mmHg. Results At the 12-month follow-up, mean IOP decreased in the PC group from 19.0 ±6.9 mmHg to 12.6 ±2.7 mmHg, and in the PDS group, from 19.1 ±5.8 mmHg to 14.3 ±3.5 mmHg ( P  < 0.05). Both groups preoperatively and at 12 months showed no significant differences in IOP ( P  > 0.05). There was no statistically significant difference between the number of medications used ( P  > 0.05). Complete and qualified success rates for both groups were 79.0 % and 76.9 % ( P  = 0.701). The most frequent postoperative PC complication was hyphema (58.0 %); for PDS, bleb fibrosis was most frequent (26.7 %). No PC patients required postoperative management. PDS patients required postoperative interventions 58.7 % of the time, including a 5-fluorouracil (5-FU) injection (58.7 %), suture lysis (48.3 %), and needling (27.6 %). Conclusions Both PC and PDS lead to an effective decrease in IOP on a short-term follow-up basis and demonstrate similar efficacy and safety profiles. PDS patients required additional procedures including 5-FU injections, suture lysis, or needling. PC patients required no additional procedures.

Purpose The success of XEN Gel Stent (XEN) and Preserflo MicroShunt (Preserflo) implantation depends mainly on the development of bleb fibrosis. This study aimed to describe the histological findings of bleb fibrosis after XEN and Preserflo surgery. Methods This retrospective study included patients with different types of glaucoma who underwent revision surgery after XEN or Preserflo implantation. The available clinical information and histological samples of removed fibrotic tissue were analyzed. Results Thirty-six patients were included. Revision surgery was performed at a median of 195 (range = 31–1264) days after primary surgery. The mean intraocular pressure changed from 29.1 (± 10.3) mmHg at baseline to 18.3 (± 8.7) mmHg (− 37%; p  < 0.0001) and 16.2 (± 4.2) mmHg (− 45%; p  < 0.0001) after 6 and 12 months, respectively. Histological analysis revealed an increase in activated fibroblasts and macrophages in all specimens and a parallel orientation of fibroblasts in a minor part of the probe in 60% of the specimens. No pronounced inflammatory reaction in the form of lymphocytic or granulocytic infiltration was observed. The comparison of specimens from uveitic glaucoma and primary open-angle glaucoma patients revealed no significant differences. Conclusions The histological analysis of fibrotic blebs from the XEN and Preserflo implants did not show any pronounced immune or foreign-body reaction and revealed a similar histological pattern of failed blebs after trabeculectomy.

Aim: To study the effectiveness of viscocanalostomy in patients with primary congenital glaucoma of the isolated trabecular dysgenesis category and compare it with trabeculotomy ab externo. Methods: Eight patients with bilateral primary congenital glaucoma were enrolled in the study. After establishing the diagnosis, the more severely affected eye was randomly selected to undergo either trabeculotomy ab externo or viscocanalostomy, whereas the second eye underwent the other surgery 2 weeks after the first. The patients were examined on day 1, week 1, week 4 and thereafter every 4 weeks. Intraocular pressure (IOP) and corneal diameter measurements were obtained at week 1, month 6 and at the last reported follow-up. The paired-sample’s Student’s t test was applied for statistical analysis. Results: The mean (standard deviation (SD)) follow-up period was 12.5 (1.86) months. Preoperative IOP of eyes undergoing trabeculotomy (34.0 (2.6) mm Hg) and that of eyes undergoing viscocanalostomy (32.3 (4.1) mm Hg) showed no significant difference (p>0.1). A drop in IOP was noted in both groups at week 1, month 6 and at the last follow-up visit (p<0.001). Similarly, a decrease in the postoperative vertical and horizontal corneal diameters was noted in the two study groups. Conclusion: Viscocanalostomy proved to be as effective as trabeculotomy ab externo in lowering IOP. Moreover, it is likely to be a good surgical alternative with a higher long-term success rate in eyes with more aggressive disease.

Purpose Incisional glaucoma surgery is indicated in advanced glaucoma or glaucoma refractory to less invasive therapies, and can be performed with implants to lower IOP including glaucoma drainage or filtration devices. The Food and Drug Administration (FDA) Manufacturer and User Facility Device Experience (MAUDE) represents the largest U.S. publicly-available repository of device-related incisional glaucoma surgery complications, enabling insight into complications experienced with incisional glaucoma surgery in real-world practice to develop a risk profile for the use of each device. Methods MAUDE database was searched between January-2012 and December-2021 for Brand Name: Ahmed ClearPath, Ahmed Glaucoma Valve, Baerveldt, Ex-PRESS, and Molteno. Reports were categorized by complication;when multiple were present, multiple categories were attributed. Reports with identical text and dates were counted as duplicate and excluded. Literature reports comparing multiple devices without clear device specification per complication were excluded. Results The search yielded 1538 reports, of which 1379 reports describing 2429 adverse events met inclusion criteria. The most common events for were hypotony/hypotony maculopathy (284), device-iris touch (282), device occlusion (213), elevated IOP (210), and device explanted due to possible exclusion (176). Delivery system failures occurred (166). Patients also experienced flat/shallow anterior chambers (147) and corneal edema/bullous keratopathy/endothelial cell count reduction/corneal decompensation/Descemet's membrane tears (128). Conclusion By drawing on the real-world complications collected in the MAUDE database, this study identifies adverse events of greatest clinical pertinence for device-related incisional glaucoma surgery overall and by brand. Understanding the most common adverse events may support surgeons in counseling patients and preparing for device implantation. Key messages What is known Incisional glaucoma surgery using glaucoma drainage devices is commonly indicated in advanced or refractory glaucoma, with the goal of lowering intraocular pressure (IOP). While adverse events have been reported by brand in controlled clinical settings, comparative literature utilizing data across multiple devices used in incisional glaucoma surgery in real-world settings is limited. What is new This study utilizes the FDA MAUDE database, the largest publicly available repository of medical device-related complications, to provide a comprehensive review of adverse events associated with devices for incisional glaucoma surgery. The study includes over 2,400 adverse events across multiple devices—including Ahmed, Ex-PRESS, and Baerveldt—offering a comparative analysis of complications across different device types in real-world settings, assisting in device selection, surgical planning, and patient counseling. The report reveals trends in device usage and reporting over time, showing a peak in adverse event reports for the Ex-PRESS device in 2014 and a decline in subsequent years, with Ahmed Glaucoma Valve and Baerveldt peaking in 2019, before a decrease suggesting changing trends in device selection and usage in clinical practice.

Post-operative fibrosis of the filtering bleb limits the success of glaucoma filtration surgery (GFS). To minimise subconjunctival scarring following GFS, treatment with antimetabolites such as Mitomycin C (MMC) has become standard practice; however, their use is associated with considerable side effects. This study aimed to investigate the anti-scarring properties of 3′,4′-dihydroxyflavonol (DiOHF). GFS was performed in New Zealand white rabbits who received eye drops of DiOHF three times daily and vehicle eye drops after surgery (n = 5) or a single intraoperative treatment of MMC (n = 5). Blebs were imaged immediately following surgery and on days 7, 15, 21, and 28 for clinical examination. On day 28, eyes were harvested to assess collagen deposition, expression of α-SMA, oxidative stress, angiogenesis, fibroblast activity, and inflammation in the conjunctiva/Tenon’s layer. At 7 and 28 days post-GFS, MMC-treated blebs were more ischaemic than DiOHF- or vehicle-treated blebs. On day 28, DiOHF treatment significantly suppressed collagen accumulation, CD31 expression, Vimentin expression, and CD45 expression compared to the vehicle control. No difference was observed in 3-Nitrotyrosine or αSMA expression between treatment groups. Treatment with DiOHF reduced conjunctival scarring and angiogenesis in rabbits with GFS, which was comparable to MMC. DiOHF may be a safer and more effective wound-modulating agent than conventional antifibrotic therapy in GFS.

Filtration bleb (FB) fibrosis represents the primary risk factor for glaucoma filtration surgery (GFS) failure. We reviewed the most recent literature on post-GFS fibrosis in humans, focusing on novel molecular pathways and antifibrotic treatments. Three main literature searches were conducted. First, we performed a narrative review of two models of extra-ocular fibrosis, idiopathic pulmonary fibrosis and skin fibrosis, to improve the comprehension of ocular fibrosis. Second, we conducted a systematic review of failed FB features in the PubMed, Embase, and Cochrane Library databases. Selected studies were screened based on the functional state and morphological features of FB. Third, we carried out a narrative review of novel potential antifibrotic molecules. In the systematic review, 11 studies met the criteria for analysis. Immunohistochemistry and genomics deemed SPARC and transglutaminases to be important for tissue remodeling and attributed pivotal roles to TGFβ and M2c macrophages in promoting FB fibrosis. Four major mechanisms were identified in the FB failure process: inflammation, fibroblast proliferation and myofibroblast conversion, vascularization, and tissue remodeling. On this basis, an updated model of FB fibrosis was described. Among the pharmacological options, particular attention was given to nintedanib, pirfenidone, and rapamycin, which are used in skin and pulmonary fibrosis, since their promising effects are demonstrated in experimental models of FB fibrosis. Based on the most recent literature, modern patho-physiological models of FB fibrosis should consider TGFβ and M2c macrophages as pivotal players and favorite targets for therapy, while research on antifibrotic strategies should clinically investigate medications utilized in the management of extra-ocular fibrosis.

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.

Conjunctival and subconjunctival fibrogenesis and inflammation are sight compromising side effects that can occur subsequent to glaucoma filtration surgery. Despite initial declines in intraocular pressure resulting from increasing aqueous outflow, one of the activated responses includes marshalling of proinflammatory and pro-fibrogenic cytokine mediator entrance into the aqueous through a sclerostomy window and their release by local cells, as well as infiltrating activated immune cells. These changes induce dysregulated inflammation, edema and extracellular matrix remodeling, which occlude outflow facility. A number of therapeutic approaches are being taken to offset declines in outflow facility since the current procedure of inhibiting fibrosis with either mitomycin C (MMC) or 5-fluorouracil (5-FU) injection is nonselective. One of them entails developing a new strategy for reducing fibrosis induced by wound healing responses including myofibroblast transdifferentiation and extracellular matrix remodeling in tissue surrounding surgically created shunts. The success of this endeavor is predicated on having a good understanding of conjunctival wound healing pathobiology. In this review, we discuss the roles of inappropriately activated growth factor and cytokine receptor linked signaling cascades inducing conjunctival fibrosis/scarring during post-glaucoma surgery wound healing. Such insight may identify drug targets for blocking fibrogenic signaling and excessive fibrosis which reduces rises in outflow facility resulting from glaucoma filtration surgery.

Objective Trabeculectomy and non-penetrating trabecular surgery are common operations for glaucoma. This meta-analysis aims to compare the effect of trabeculectomy and non-penetrating trabecular surgery in postoperative astigmatism of patients with glaucoma. Methods A systematic literature search was performed for studies comparing trabeculectomy and non-penetrating trabecular surgery in patients with glaucoma. The time frame for the search was from the time of construction to April 2024. There were no restrictions regarding study type or type of glaucoma. The endpoint was the surgically induced astigmatism assessed 6 months after operation. We conducted this meta-analysis following the PRISMA (Preferred Reporting Items for Systematic Review and Meta-Analysis). Results Five eligible studies were included in this meta-analysis and presented data for 359 eyes with various types of glaucoma at different stages. The results revealed an increase in astigmatism in patients with glaucoma after trabeculectomy and non-penetrating trabecular surgery. Trabeculectomy had a higher incidence of astigmatism than in the non-penetrating trabecular surgery group at or around 6 months postoperatively, and the difference was statistically significant. (SMD = 0.40, 95% CI = 0.19 to 0.61, P  = 0.02). Conclusion Our results demonstrated that both trabeculectomy and non-penetrating trabecular surgery could increase astigmatism until 6 months after operation. Moreover, non-penetrating trabecular surgery group seems to have less influence on astigmatism. Trial registration number CRD42024517708.

Glaucoma filtration surgery is one of the most effective methods for lowering intraocular pressure in glaucoma. The surgery efficiently reduces intra-ocular pressure but the most common cause of failure is scarring at the incision site. This occurs in the conjunctiva/Tenon's capsule layer overlying the scleral coat of the eye. Currently used antimetabolite treatments to prevent post-surgical scarring are non-selective and are associated with potentially blinding side effects. Developing new treatments to target scarring requires both a better understanding of wound healing and scarring in the conjunctiva, and new means of delivering anti-scarring drugs locally and sustainably. By combining plastic compression of collagen gels with a soft collagen-based layer, we have developed a physiologically relevant model of the sub-epithelial bulbar conjunctiva/Tenon's capsule interface, which allows a more holistic approach to the understanding of subconjunctival tissue behaviour and local drug delivery. The biomimetic tissue hosts both primary human conjunctival fibroblasts and an immune component in the form of macrophages, morphologically and structurally mimicking the mechanical proprieties and contraction kinetics of ex vivo porcine conjunctiva. We show that our model is suitable for the screening of drugs targeting scarring and/or inflammation, and amenable to the study of local drug delivery devices that can be inserted in between the two layers of the biomimetic. We propose that this multicellular-bilayer engineered tissue will be useful to study complex biological aspects of scarring and fibrosis, including the role of inflammation, with potentially significant implications for the management of scarring following glaucoma filtration surgery and other anterior ocular segment scarring conditions. Crucially, it uniquely allows the evaluation of new means of local drug delivery within a physiologically relevant tissue mimetic, mimicking intraoperative drug delivery in vivo.