Search Results (11)

Background/Objectives: This work aims to clarify whether the subtenon use of the sodium hyaluronate product Healaflow in filtrating surgery with PreserFlo MicroShunt positively influences the early postoperative course in terms of control of intraocular pressure, hypotony, and needling rate. Methods: A retrospective, randomized controlled, interventional, single-center trial was performed at the Ludwig Maximilians-University Munich from January 2024 to July 2024. Only patients with primary open angle glaucoma (POAG) were included. In all patients, a complete ophthalmological examination including best corrected visual acuity (BCVA), automated refraction, and Goldman tonometry was performed at 2 days, 1–4 and 5–8 weeks, and 3–4 and 5–6 months after surgery. Healaflow was injected underneath the tenon during filtrating surgery with PreserFlo MicroShunt in addition to mitomycin C (MMC). The Healaflow group was compared to a control group with POAG patients in which Healaflow was not used during surgery with PreserFlo MicroShunt and MMC. Results: A total of 45 eyes of 45 patients were included, with 20 eyes in the Healaflow group and 25 eyes in the control group. In both groups, a significant reduction in IOP and medication could be observed: complete surgical success (IOP ≥ 6 mm Hg and ≤17 mm Hg, without surgical complications or complete loss of vision) was reached in 88% of patients in the Healaflow group at the last follow-up. In 95% of patients in the control group, complete success could be observed. The success rates did not significantly differ between the two groups (p = 0.568). Hypotony rates were 35% in the Healaflow and 12% in the control group after two days (p = 0.083); the rates equalized after 1–4 weeks (p = 1). Needling rates were comparable between both groups (25% versus 20%, p = 0.731). Conclusions: PreserFlo MicroShunt implantation with MMC was equally effective in terms of reduction in IOP and medication in both scenarios with additional or without the use of Healaflow. Postoperative hypotony and needling rates did not significantly differ between the two groups. The additional effects of Healaflow on anti-scarring and maintaining space are likely too minimal to cause significant differences in IOP or medication when already treated with MMC. Full article

Objectives: We evaluated the 3-year effectiveness and safety of XEN45, combined or not with phacoemulsification, in patients from the Italian XEN-Glaucoma Treatment Registry. Methods: Data from glaucoma patients who underwent XEN45 alone or combined with phacoemulsification were analyzed. Changes in intraocular pressure (IOP) and the number of ocular hypotensive medications (OHMs) were tested with repeated measures ANOVA in last observation carried forward (LOCF) and per-protocol (PP) analyses. Complete and qualified success (IOP < 18 mmHg and ≥20% IOP reduction from baseline, without or with OHMs) at 36 months and pre- and intraoperative factors predicting surgery failure were explored using survival analysis and Cox proportional-hazard models. Complications rates were evaluated to assess safety. Results: The analysis included 239 eyes (239 patients): 144 (60.2%) in the XEN alone and 95 (39.8%) in the XEN+Phaco groups. Overall success was achieved in 164 (68.1%) eyes [113 (68.9%) complete and 51 (31.1%) qualified], without significant differences in success (p = 0.07) and survival rates (p = 0.46) between groups. At the 36th month, the baseline IOP decreased from a median (IQR) of 23.0 (20.0–26.0) to 15.0 (12.0–17.5) mmHg (p < 0.01), with an overall 34.1 ± 20.1% IOP reduction. The mean ± SD number of OHMs decreased from the baseline of 2.7 ± 0.9 to 0.9 ± 1.1 at month 36 (p < 0.01). PP and LOCF analyses were comparable. Neither pre- nor intraoperative factors were significantly predictive of surgery failure. In 91 (38.1%) and 57 (23.8%) of the eyes, at least one postoperative complication occurred early (<month 1) and late (≥month 1) during follow-up, respectively, without sequelae. During follow-up, 68 (28.5%) eyes needed at least one needling. Conclusions: At 3 years, XEN45, combined or not with phacoemulsification, effectively and safely reduced IOP and OHMs need. Full article

Objectives: This study aimed to evaluate the postoperative outcomes of the PreserFlo MicroShunt in Asian patients with exfoliation glaucoma. Methods: We used the Kaplan–Meier method to analyze 29 eyes of 29 patients with exfoliation glaucoma (mean age: 80.7 ± 8.3 years; 16 males; 24 eyes with intraocular lens implants; preoperative intraocular pressure [IOP]: 32.5 ± 9.3 mmHg; preoperative antiglaucoma medications: 3.4 ± 1.0; Asian ethnicity: 100%) who underwent PreserFlo MicroShunt surgery alone at Saneikai Tsukazaki Hospital from November 2022 to November 2023. The criteria for survival were a reduction in IOP of ≥20%, no additional glaucoma surgery, and IOP of 5–21 mmHg (condition 1), 5–18 mmHg (condition 2), and 5–15 mmHg (condition 3). Needling and glaucoma eye drops were considered qualified successes. Results: The mean follow-up period was 27.9 weeks, with a reoperation rate of 31% (9 cases). The complete and qualified success survival rates at 24 weeks were 56%, 52%, and 49%, and 67%, 59%, and 53% for conditions 1–3, respectively. The complete and qualified success survival rates at 48 weeks were 47%, 43%, and 45%, and 52%, 46%, and 48% for conditions 1–3, respectively. Conclusions: The postoperative outcomes of the PreserFlo MicroShunt in Asian patients with exfoliation glaucoma demonstrated an approximate 50% success rate at both 24 and 48 weeks, with a reoperation rate of approximately 30%. Caution is warranted when performing PreserFlo MicroShunt in patients with exfoliation glaucoma. Full article

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. Full article

Distal outflow bleb-forming procedures in ophthalmic surgery expose subconjunctival tissue to inflammatory cytokines present in the aqueous humor, resulting in impaired outflow and, consequently, increased intraocular pressure. Clinically, this manifests as an increased risk of surgical failure often necessitating revision. This study (1) introduces a novel high-throughput screening platform for testing potential anti-fibrotic compounds and (2) assesses the clinical viability of modulating the transforming growth factor beta-SMAD2/3 pathway as a key contributor to post-operative outflow reduction, using the signal transduction inhibitor verteporfin. Human Tenon’s capsule fibroblasts (HTCFs) were cultured within a 3D collagen matrix in a microfluidic system modelling aqueous humor drainage. The perfusate was augmented with transforming growth factor beta 1 (TGFβ1), and afferent pressure to the tissue-mimetic was continuously monitored to detect treatment-related pressure elevations. Co-treatment with verteporfin was employed to evaluate its capacity to counteract TGFβ1 induced pressure changes. Immunofluorescent studies were conducted on the tissue-mimetic to corroborate the pressure data with cellular changes. Introduction of TGFβ1 induced treatment-related afferent pressure increase in the tissue-mimetic. HTCFs treated with TGFβ1 displayed visibly enlarged cytoskeletons and stress fiber formation, consistent with myofibroblast transformation. Importantly, verteporfin effectively mitigated these changes, reducing both afferent pressure increases and cytoskeletal alterations. In summary, this study models the pathological filtration bleb response to TGFβ1, while demonstrating verteporfin’s effectiveness in ameliorating both functional and cellular changes caused by TGFβ1. These demonstrate modulation of the aforementioned pathway as a potential avenue for addressing post-operative changes and reductions in filtration bleb outflow capacity. Furthermore, the establishment of a high-throughput screening platform offers a valuable pre-animal testing tool for investigating potential compounds to facilitate surgical wound healing. Full article

Scar formation resulting from overly active wound healing is a critical factor in the success rate of glaucoma filtration surgery (GFS). IL-6 and TGF-β have been implicated in the pathogenesis of fibrogenesis. In addition, the signal transducer and activator of transcription 3 (STAT3) can be activated by numerous cytokines and growth factors, including IL-6 and TGF-β1. Thus, STAT3 activation may integrate common profibrotic pathways to promote fibrosis. In this study, an increase in p-STAT3 was observed in activated HTFs. Inhibiting STAT3 in cultured HTFs by pharmacological inactivation reversed the fibrotic responses, such as fibroblast migration, the differentiation of resting fibroblasts into myofibroblasts and the deposition of ECM, mediated by IL-6 and TGF-β1. Moreover, the expression of suppressor of cytokine signaling 3 (SOCS3) was decreased in HTFs cultured with IL-6 and TGF-β1, and SOCS3 overexpression rescued ECM deposition, α-SMA expression and migration in IL-6- and TGF-β1-stimulated HTFs by inactivating STAT3. Finally, S3I-201 treatment inhibited profibrotic gene expression and subconjunctival fibrosis in a rat model of GFS. In conclusion, our data suggests that STAT3 plays a central role in fibrosis induced by different profibrotic pathways and that STAT3 is a potential target for antifibrotic therapies following GFS. Full article

The early failure of glaucoma surgery is mainly caused by over-fibrosis at the subconjunctival space, causing obliteration of the filtration bleb. Because fibrosis has a suspected basis of genetic predisposition, we have undertaken a prospective study to identify upregulated profibrotic genes in a population of glaucoma patients with signs of conjunctival fibrosis and early postoperative surgical failure. Clinical data of re-operated fibrosis patients, hyperfibrosis patients who re-operated more than once in a short time, and control patients with no fibrosis were recorded and analyzed at each follow-up visit. Conjunctival-Tenon surgical specimens were obtained intraoperatively to evaluate the local expression of a panel of genes potentially associated with fibrosis. In order to correlate gene expression signatures with protein levels, we quantified secreted proteins in primary cultures of fibroblasts from patients. Expression of VEGFA, CXCL8, MYC, and CDKN1A was induced in the conjunctiva of hyperfibrosis patients. VEGFA and IL8 protein levels were also increased in fibroblast supernatants. We propose that an increase in these proteins could be useful in detecting conjunctival fibrosis in glaucoma patients undergoing filtering surgery. Molecular markers could be crucial for early detection of patients at high risk of failure of filtration surgery, leading to more optimal and personalized treatments. Full article

Background: To evaluate the long-term efficacy and safety of modified canaloplasty versus trabeculectomy in open-angle glaucoma. Methods: In total, 210 subjects with open-angle glaucoma were included. 70 were treated with Mitomycin C-augmented modified canaloplasty with enhanced subconjunctival filtration and 140 with Mitomycin C-augmented trabeculectomy. Cases were matched 1:2 by sex and age. Results: In canaloplasty and trabeculectomy groups, 61.4% and 57.9% of participants were female. Mean age was 60.0 ± 13.9 and 63.0 ± 12.2 years, median follow-up time was 4.6 [IQR 4.3, 5.05] years and 5.8 [IQR 5.4, 6.3]. Strict success was achieved in 20.0% and 56.4%, complete success in 24.3% and 66.4%, and qualified success in 34.3% and 73.6% (each p < 0.001). Kaplan–Meier survival analysis showed a better survival probability for trabeculectomy than for canaloplasty (p < 0.001) and Cox regression analysis revealed an HR of 6.03 (95%-CI 3.66, 9.93, p < 0.001) after canaloplasty. Trabeculectomy showed superiority in terms of IOP decrease (9.2 ± 7.9 mmHg vs. 13.7 ± 10.4 mmHg, p = 0.002), use of AGM (50.0% vs. 10.7%, p < 0.001), and the number of revision surgeries (41.4% vs. 21.4%, p = 0.004). Occurrence of complications was similar in both groups (14.5% vs. 7.5%, p = 0.19). Conclusions: Trabeculectomy showed superiority in efficacy and equality in safety compared to modified canaloplasty. Full article

Collagen accumulation in sub-conjunctival tissue at the surgical wound is one of the major complications associated with glaucoma filtration surgery (GFS). This process often leads to unwanted fibrotic scar formation at the lesion site and dysfunction of tissues. Previously, we demonstrated that NADPH oxidase 4 (Nox4) is implicated in transforming growth factor-beta (TGFβ)-induced collagen production in ocular fibroblasts and scarring responses in a mouse model of corneal injury. Here, we propose that Nox4 is an important facilitator of TGFβ-induced responses. We tested this hypothesis in human Tenon’s fibroblasts (HTF) and also assessed a role of Nox4 in an experimental mouse model of GFS. TGFβ1 induced Nox4 mRNA expression but downregulated Nox5 in HTF. Targeting Nox4 gene expression with an adenovirus carrying a Nox4 small interfering RNA (siRNA) (Ad-Nox4i) or removal of hydrogen peroxide (H₂O₂) with EUK-134 (25 μM) in HTFs significantly reduced TGFβ1-induced Nox4 expression, H₂O₂ production, and collagen synthesis (p < 0.05, n = 3–6). SIS3 (5 μM) that prevents Smad3 phosphorylation is found to suppress TGFβ1-induced collagen production in HTFs. Furthermore, Ad-Nox4i and EUK-134 both abolished TGFβ1-stimulated proliferation of HTFs. We also compared collagen deposition at the wound arising from GFS between wildtype (WT) and Nox4 knockout (KO) mice. Both collagen deposition and fibrovascularization at the wound were significantly decreased in Nox4 KO mice at 14 days after GFS. Our results provide comprehensive evidence that Nox4 is an important mediator for TGFβ1-induced responses in HTFs and collagen deposition in surgical wound following GFS in mice. As such, pharmacological inhibition of Nox4 would be a viable therapeutic strategy for the control of scarring after glaucoma surgery. Full article

Regorafenib eye drops were developed for treating age-related macular degeneration. This study aimed to investigate the effects of this multi-kinase inhibitor on intraocular pressure (IOP), bleb formation, and conjunctival changes in a canine filtration surgery model. Glaucoma filtration surgery models were created in 24 eyes of 24 beagles. In experiment 1 (Ex 1), regorafenib eye drops (regorafenib group: n = 6) or a vehicle (control group, n = 6) were instilled twice daily for 4 weeks postoperatively. In experiment 2 (Ex 2), regorafenib eye drops were instilled as in Ex 1 (regorafenib group: n = 6) for 12 weeks while conventional intraoperative mitomycin-C (MMC) was utilized (MMC group: n = 6), In Ex 1, only the regorafenib group showed significant IOP reduction with a significantly higher bleb score. Subconjunctival area, collagen density, vessels, and cells showing proliferation and differentiation were lower in subconjunctival tissue in the regorafenib group. In Ex 2, no significant difference was found in IOP reduction and bleb formation between the regorafenib and MMC groups; bleb walls were significantly thicker and collagen density and vessels were higher in the regorafenib group; and no differences were observed in the above-mentioned cells. Thus, regorafenib might be a better alternative to MMC for creating thicker and less ischemic blebs in glaucoma filtration surgery. Full article

In this present study, we investigated the effect of a controlled release of anti-transforming growth factor β (TGF-β) antibody on intraocular pressure (IOP), bleb formation, and conjunctival scarring in a canine glaucoma filtration surgery model using gelatin hydrogel (GH). Glaucoma surgery models were made in 14 eyes of 14 beagles and divided into the following two groups: (1) subconjunctival implantation of anti-TGF-β antibody-loaded GH (GH-TGF-β group, n = 7), and (2) subconjunctival implantation of GH alone (GH group, n = 7). IOP and bleb features were then assessed in each eye at 2- and 4-weeks postoperative, followed by histological evaluation. We found that IOP was significantly reduced at 4-weeks postoperative in the two groups (p < 0.05) and that IOP in the GH-TGF-β-group eyes was significantly lower than that in the GH-group eyes (p = 0.006). In addition, the bleb score at 4-weeks postoperative was significantly higher in the GH-TGF-β group than in the GH group (p < 0.05), and the densities of fibroblasts, proliferative-cell nuclear antigen (PCNA)-positive cells, mast cells, and TGF-β-positive cells were significantly lower in the GH-TGF-β group than in the GH group. The findings of this study suggest that, compared with the GH-group eyes, implantation of anti-TGF-β antibody-loaded GH maintains IOP reduction and bleb formation by suppressing conjunctival scarring due to the proliferation of fibroblasts for a longer time period via a sustained release of anti-TGF-β antibody from GH. Full article