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.

Background/objectives: The efficacy and safety of the XEN45 gel stent implant in patients with glaucoma have been amply demonstrated. XEN63 is a new device that has been developed with a larger bore. This multicenter, observational, retrospective study assessed the efficacy and safety of XEN63 in patients with glaucoma. Methods: Medical records from six participating centers were screened to identify patients meeting the inclusion criteria. The primary outcome was mean IOP at 6 months after surgery. Results: The study included 114 eyes from 102 patients (XEN63 alone: 68 eyes, and XEN63 + Phaco: 46 eyes); 92% of patients had primary open-angle glaucoma. Baseline IOP for all patients was a median of 23.0 mmHg (IQR: 18.5–27.5 mmHg), which decreased significantly on day one post-surgery to 7.0 mmHg (IQR: 4.5–9.5 mmHg) and gradually stabilized at around 13.5 mmHg (IQR: 10.5–16.5 mmHg) by 6 months with no significant differences between groups at 6 months. The number of ocular hypertensive medications (OHMs) reduced significantly from a baseline median of 2.7 ± 1.1 to 0.5 ± 1.0 at 6 months in the entire cohort. The XEN63 alone group showed a significantly lower need for OHMs at 3 and 6 months. The surgical success rate was comparable between the two groups (54.4% vs. 47.8%, p = 0.05, XEN63 alone and XEN63 + Phaco). There was no statistically significant difference in survival outcomes between the XEN63 (0.59, 95% CI: 0.49–0.73) and XEN63 + Phaco groups (0.55, 95% CI: 0.42–0.72) (p = 0.89). Conclusions: In the largest study with XEN63 to date, the device appears to significantly decrease the IOP and the OHMs. Simultaneous XEN63 implant and phacoemulsification showed similar outcomes compared to XEN63 alone.

To assess the long-term (4 year) outcomes of staged (phacoemulsification \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} $$ \ge $$6 months prior to trabeculectomy) or combined (phacotrabeculectomy) surgical approaches in patients with uncontrolled glaucoma. Patients who underwent trabeculectomy alone (with phacoemulsification at least 6 months before trabeculectomy - staged approach) and simultaneous phacotrabeculectomy (combined approach) were included in this retrospective chart review study. Surgical success was defined as complete (without medication) or qualified (with medication) according to 3 criteria of upper limits: intraocular pressure (IOP) > 21 mmHg (criterion A), > 18 mmHg (B), > 15 mmHg (C). Mean IOP values were compared between groups at each follow-up. A total of 72 patients (staged n = 35, combined n = 37) were included. No differences in baseline characteristics were observed between groups. The mean age was 72.3 years, almost three-quarters were diagnosed with primary open-angle glaucoma (73.6%), and mean baseline IOP was 26.4 ± 7.2. Mean IOP significantly decreased in both groups. After 4 years of follow-up, patients in the staged group had a significantly lower mean IOP (10.9 ±3.6 vs. 14.8 ± 6.2, p 0.002), a higher surgical success rate according to each criterion, and a lower need of postoperative drugs and manipulation compared to the combined approach. In this study comparing staged and simultaneous approaches with the longest follow-up to date, patients with cataract and glaucoma experience a substantial and comparable reduction in IOP from baseline after both approaches. The analysis is mainly limited by its retrospective, non-randomized design. However, compared to simultaneous phacotrabeculectomy, the staged approach was associated with lower final IOP, higher long-term surgical success, and fewer postoperative interventions.