RARE DISEASE
Scarring in glaucoma filtration surgical procedures
Scarring in glaucoma filtration surgical procedures
Scarring in glaucoma filtration surgical procedures
Drug discovery
5
drugs
With orphan designations
Overview
Scarring in glaucoma filtration surgical procedures occurs due to excessive fibrosis at the surgical site, often leading to bleb failure, elevated intraocular pressure (IOP), and vision loss. This scarring typically arises from fibroblast activation during postoperative healing, with failure rates reaching 30% at 3 years and 50% at 5 years despite anti-scarring interventions [2][5][16]. Current strategies focus on modulating wound healing using antimetabolites and novel agents to prolong bleb survival [2][4][8].
Therapies
Intra/postoperative antimetabolites: Mitomycin C (MMC) and 5-fluorouracil (5-FU) to inhibit fibroblast proliferation [2][16][5].
Adjunctive anti-VEGF agents (e.g., bevacizumab) to reduce angiogenesis and fibrosis [4][7][9].
Needle revision with anti-scarring drugs for bleb rescue [4][9]. Emerging therapies target growth factors (e.g., TGF-β) and biomechanical pathways [8][12][17].
Categories: rare ophthalmic disorders
Research Papers
1,248 drug discovery papers about Scarring in glaucoma filtration surgical procedures, with 1 first-in-class and 2 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
1,248 drug discovery papers about Scarring in glaucoma filtration surgical procedures, with 1 first-in-class and 2 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
categories:
Small molecules
small molecules
2026-02-02 | STING deficiency alleviates scar formation after glaucoma filtration surgery by suppressing p38 MAPK-induced inflammation in mice.
Glaucoma filtration surgery (GFS) often fails because of excessive scar formation driven by inflammation and fibroblast activation. Although the stimulator of interferon genes (STING) pathway is involved in inflammatory responses, its role in post-surgical fibrosis remains unclear. A mouse GFS model was established in wild-type (WT) and STING-knockout (STING-KO) animals. A parallel cohort of WT mice received a single intraoperative subconjunctival injection of the STING inhibitor H151. Bleb survival, intraocular pressure, histopathology, collagen deposition, and inflammatory/fibrotic markers were evaluated for 28 days. RNA sequencing, Western blotting, and ELISA were employed to profile the p38/MAPK axis. Primary human Tenon's capsule fibroblasts were treated with angiotensin II in the presence or absence of STING silencing or H151 to corroborate mechanisms in vitro. STING expression was markedly up-regulated in fibroblasts within human and mice post-GFS tissues. STING-KO mice exhibited prolonged bleb survival together with reduced collagen deposition and fibroblast activation. RNA-sequencing revealed that STING deletion significantly altered the p38 mitogen-activated protein kinase (MAPK) pathway. Mechanistically, STING deficiency suppressed p38 MAPK phosphorylation, leading to decreased levels of the pro-inflammatory cytokines interleukin-6 (IL-6), tumor necrosis factor-α, IL-18, and IL-1β, as well as the fibrogenic factors α-SMA, collagen I, fibronectin, connective tissue growth factor, and collagen type III alpha 1 at the surgical sites. Consistently, the selective STING inhibitor H151 recapitulated these effects by suppressing p38 MAPK signaling and markedly reducing fibrotic scarring. STING deficiency alleviates scar formation after GFS by suppressing p38 MAPK pathway. Targeting STING/p38 axis may improve surgical outcomes by modulating the balance between inflammation and tissue repair.
2026-01-13 | Factors influencing the long-term-success of the XEN gel stent.
PURPOSE: The XEN gel stent is a minimally invasive surgical device for patients with open-angle glaucoma, developed to reduce complications associated with traditional filtration surgery. This study aimed to identify clinical factors that influence long-term surgical success, particularly in the context of postoperative conjunctival scarring. METHODS: In this retrospective study, 773 eyes of patients with glaucoma treated at a tertiary care center underwent implantation of the XEN gel stent. The primary outcome was long-term surgical success, defined as a reduction in intraocular pressure of at least 20% and achieving a target pressure of 18, 15, or 12 mmHg, either without (complete) or with (qualified) medication. Secondary outcomes included intraocular pressure reduction, change in best-corrected visual acuity and medication use. Potential risk factors were analysed using Kaplan-Meier survival curves and multivariable Cox regression. RESULTS: At 24 months, complete and qualified success for a target pressure of 18 mmHg was achieved in 50% and 64% of cases, respectively; at 72 months, in 35% and 54%. Visual acuity remained stable. Female sex, mitomycin C dose, moderately elevated baseline pressure, and lower pressure on the first postoperative day were associated with significantly higher success rates (p < 0.05). Glaucoma subtype and previous incisional glaucoma surgery had no significant effect. CONCLUSION: Sex, lower antimetabolite dose and intraocular pressure values before and shortly after surgery are significant predictors of long-term success following XEN gel stent implantation.
2025-08-29 | A Suturable and Drug-Free Polyzwitterionic Hydrogel for Alleviating Scar Formation After Glaucoma Filtration Surgery.
Glaucoma stands as a leading cause of irreversible blindness worldwide. Glaucoma filtration surgery (GFS) is the main surgical approach for its treatment. However, postoperative inflammation or immune responses can stimulate excessive scar formation, compromising surgical outcomes and potentially leading to complications such as uncontrolled intraocular pressure (IOP). This study aimed to develop a suturable polyzwitterionic hydrogel by combining 2-((2-hydroxy-3-(methacryloyloxy) propyl) dimethyl ammonio) acetate (CBOH), a zwitterionic monomer containing hydroxyl groups, with 2-hydroxyethyl methacrylate (HEMA) to prevent GFS-induced scar formation. The introduction of the CBOH component imparts excellent antifouling properties and a relatively low modulus, giving it mechanical characteristics similar to native ocular tissue. This facilitates the prevention of scar tissue formation following GFS and reduces foreign body sensation caused by long-term implant materials. In an animal model of GFS, P(HEMA-CBOH) hydrogel maintained filtration bleb survival and lowered IOP for up to 4 weeks postoperatively. Furturemore, it reduced collagen deposition and α-SMA expression within conjunctival and scleral tissue, demonstrating their efficacy in inhibiting scar formation and improving GFS outcomes. Overall, as a suturable, drug-free polyzwitterionic hydrogel, P(HEMA-CBOH) holds significant potential for clinical applications in GFS, largely due to its inherent antifouling properties.
2025-07-16 | Inhibitory Effects of 3',4'-Dihydroxyflavonol in a Rabbit Model of Minimally Invasive Bleb Surgery With PreserFlo MicroShunt.
The success of minimally invasive bleb surgery (MIBS) such as the PreserFlo MicroShunt (PFMS) is limited by post-operative bleb fibrosis. Current clinical practice prescribes the use of off-label cytotoxic antimetabolites such as Mitomycin C (MMC) as antifibrotic therapy. This study investigates the anti-scarring properties of a novel compound, 3',4'-Dihydroxyflavonol (DiOHF) in a rabbit model of PFMS filtration surgery. Fifteen New Zealand white rabbits underwent unilateral MIBS with PFMS. Treatment was randomised to the following groups: (1) vehicle (n = 5), (2) DiOHF (n = 5), both applied three times daily for 2 weeks or (3) a single dose of MMC administered intraoperatively (n = 5). Blebs were photographed post-operatively on Days 0, 7 and 14 for clinical examination. Eyes were harvested on Day 14 and processed for immunohistochemical tissue staining to assess collagen deposition, expression of αSMA, oxidative stress, fibroblast activity, angiogenesis and inflammation in the conjunctiva/Tenon's layer. At 2-weeks post-surgery, MMC blebs were larger and more ischaemic than other treatments (Bleb size: MMC vs. DiOHF, p = 0.0098; MMC vs. vehicle, p = 0.0001. Ischaemia: p = 0.0004 for both). Compared to vehicle control, DiOHF blebs expressed decreased vimentin (p = 0.0099), αSMA (p = 0.0231) and 3-nitrotyrosine (p = 0.0410) after 2 weeks. DiOHF blebs expressed less CD45 than other treatments (DiOHF vs. Vehicle, p = 0.0013; DiOHF vs. MMC, p = 0.0232) and less collagen accumulation (DiOHF vs. vehicle, p = 0.0512). There was no difference in CD31 expression between treatment groups. DiOHF inhibited scarring following implantation of PFMS in rabbit eyes by reducing local oxidative stress, inflammation and fibroblastic activity. DiOHF may be a safer and more effective wound modulating agent than the conventional use of MMC.
2024-10-16 | 3',4'-Dihydroxyflavonol Inhibits Fibrotic Response in a Rabbit Model of Glaucoma Filtration Surgery.
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.
antibodies
2024-12-02 | Targeting CCL5 Attenuates Fibrosis via Activation of PI3k/Akt Signaling Axis After Glaucoma Filtration Surgery.
Glaucoma filtration surgery (GFS) stands as a paramount clinical intervention for glaucoma. Nonetheless, the prevalent cause of GFS failure is filtration bleb scarring, and the role of inflammation and immune response in contributing to fibrosis remains elusive. The study employed 30 female Sprague-Dawley rats (8 weeks old, 200-250 g) to assess the anti-scarring impact of the Chemokine (C-C motif) receptor 5 (CCR5)-Chemokine (C-C motif) ligand 5 (CCL5) antibody after GFS. Additionally, anti-fibrotic effects on HConFs were examined, creating an intra-operative inflammatory response using damaged-HConFs supernatant medium (DHSM). In vitro and in vivo validation aimed to elucidate the potential anti-fibrotic molecular mechanism of the CCR5-CCL5 antibody. The CCR5-CCL5 antibody effectively prolonged filtration bleb duration and enhanced the functionality of the filtered bleb. Improved postoperative intraocular pressure values (IOP) and morphological images were observed in the CCR5-CCL5 antibody-treated group. Histochemical staining and cellular experiments confirmed the antifibrotic function of the CCR5-CCL5 antibody. Notably, M2-type macrophage polarization was reduced in the CCR5-CCL5 antibody-treated model. CCL5-induced fibrosis in HConFs was mediated through the PI3K/Akt signaling pathway. Consistently, inhibition of PI3K/Akt significantly attenuated the profibrotic effects of CCR5-CCL5. Mechanistically, the CCL5 antibody exerts its antifibrotic effect by targeting CCR5 on HConFs, leading to the inhibition of the PI3K/Akt mechanism. This study unveils that CCR5-CCL5 promotes fibrosis in GFS through inflammatory stimulation of HConFs and enhanced activation of the PI3K/Akt signaling pathway. The findings suggest that intraoperative CCR5-CCL5 antibody treatment could serve as a cost-effective therapeutic agent or a useful adjuvant in preventing ocular bleb scar formation.
2024-10-26 | Conjunctival Advancement Procedure for Repairing Conjunctival Exposure of the PreserFlo MicroShunt
A 59-year-old Japanese woman with primary open-angle glaucoma underwent PreserFlo MicroShunt (PFM) (Santen Pharmaceutical Co., Ltd., Osaka, Japan) implantation in her left eye. Six weeks postoperatively, a conjunctival exposure of the posterior end of the device was observed, accompanied by aqueous leakage. The patient had no identifiable risk factors for exposure, such as previous conjunctival incisional surgeries, significant blepharitis, or needling procedures. Conjunctival advancement surgery was performed to cover the exposed device. After the sufficient dissection of scar tissue surrounding the PFM and the reapproximation of the conjunctiva, the device was successfully covered. Postoperatively, the filtration bleb remained formed, and the intraocular pressure (IOP) was controlled. No recurrence of device exposure was observed after 18 months of follow-up. Although PFM device exposure is a rare complication, it requires prompt surgical intervention to prevent infection and maintain IOP control. Conjunctival advancement surgery is an effective treatment option that allows for the repair of the exposure while preserving the filtration function of the device.
2024-03-01 | Evaluation of The Efficacy of Aflibercept versus Mitomycin C in Trabeculectomy in Cases of Primary Open Angle Glaucoma
Background: Post-operative scarring at the bleb site is a major factor in whether or not a trabeculectomy is successful. Mitomycin C and anti-vascular endothelial growth factor drugs like Aflibercept have been frequently used as supplementary treatments to trabeculectomy.Aim of the Study: This study aims to compare the efficacy of aflibercept and mitomycin c in trabeculectomy in patients with primary open-angle glaucoma.Patients and Methods: This prospective interventional study was carried out in Al-Azhar University Hospital in New Damietta from 2021 to 2023 on 40 patients with uncontrollable bilateral primary open angle glaucoma. Patients were divided into 2 groups each patient was represented in each group with one eye: Group 1, Included 20 eyes with medically uncontrolled primary open-angle glaucoma in which sub scleral trabeculectomy with intraoperative mitomycin C [0.3mg/1ml] topical application was done. Group 2, Included 20 eyes with medically uncontrolled primary open-angle glaucoma in which subscleral trabeculectomy with intraoperative subconjunctival single dose of Eylea [2 mg / 0.05 mL] was done.Results: According to the IOP, we found a statistically significant reduction in the IOP from 25 [23-28] mmHg in group 1 and 25 [23-28] mmHg in group 2 at the baseline to 14 [13-15] mmHg in group 1 and 16 [15-16] mmHg in group 2 at 12 months postoperative [P = 0.001]. In terms of the Bleb evaluation, the Mainz score was used for the Bleb assessment all over the follow-up periods. It consists of seven main domains, bleb height, peripheral vascularity, central vascularity, transparency, microcyst formation, and conjunctival mobility. We found no statistically significant difference between the 2 groups as regards all Mainz domains over the follow-up periods [P > 0.05 for all].Conclusion: The use of intraoperative subconjunctival single-dose Aflibercept in trabeculectomy is safe effective and comparable to the use of MMC in terms of the advantage of avoiding the potentially dangerous complications related to MMC use.
2023-09-04 | Treatment of filtration bleb dysfunction after glaucoma surgery by needle revision of filtration bleb combined with conbercept.
Filtration surgery (Trabeculectomy) is the main treatment for glaucoma. The scarring of the filtration bleb and obstruction of the outflow of aqueous humor through the filtration channel are the main reasons of the surgery failure. The objective of this study was to determine the clinical efficacy of needle revision of filtration blebs combined with subconjunctival injection of conbercept on the functional bleb formation in glaucoma patients with eye pressure out of control after trabeculectomy. A total of 48 eyes with poor filtration bleb function after trabeculectomy for glaucoma were treated with needle revision of filtration bleb combined with subconjunctival injection of conbercept. After the treatment, the patients were followed up for 3 months during which visual acuity, intraocular pressure, slit lamp and ultrasound biomicroscope examinations were performed. Intraoperative and postoperative complications were recorded. The visual acuity and intraocular pressure were significantly improved after the needle revision of filtration blebs. Among the 48 eyes, 39 eyes still had functional blebs at the end of the follow-up period, and filtration blebs failed in 9 eyes 2 to 8 weeks after the removal of the needle. The survival rate of filtration blebs at 3 months after needle revision was (79.06 ± 3.42%), and 81.25% (39/48) of the eyes showed good formation rate of functional bleb at the last follow-up. Three months after needle revision, there was local scar formation in some filtration blebs. Part of the filtration blebs showed mild thickening of the local subconjunctival tissue, and the filtration bleb was slightly raised and diffuse, showing a multi-cavity and thin-walled shape in some blebs. Ultrasound biomicroscopy examination showed relative structural manifestations. Subconjunctival hemorrhage occurred in 43 patients during and after the operation. Low intraocular pressure occurred in 8 patients with the lowest pressure of 5 mm Hg. Choroidal edema was observed in 3 patients. Five patients had intraoperative conjunctival hemorrhage in the anterior chamber, and hyphema occurred. All complications were self-limited and resolved without surgical intervention. Needle revision of filtration bleb combined with anti-VEGF drugs is a safe and effective method for the treatment of filtration bleb dysfunction after surgery of glaucoma.
2023-08-04 | Intravitreal bevacizumab improves trabeculectomy survival at 12 months: the bevacizumab in trabeculectomy study—a randomised clinical trial
Aims To evaluate the effect of an intraoperative dose of intravitreal bevacizumab (Avastin) on surgical success following trabeculectomy with mitomycin-C (MMC) over 12 months. Methods A single centre, parallel, double-blinded randomised, placebo-controlled trial recruiting patients requiring trabeculectomy for progressing glaucoma. Patients were randomised to intravitreal bevacizumab or placebo. Main outcome measure The primary outcome of treatment success was defined by ‘complete success’ when intraocular pressure (IOP) remained less than a predefined target IOP without the requirement of topical medication, or ‘qualified success’ where topical medication was required to meet the predefined target IOP threshold. Secondary outcomes included the need for subsequent IOP-lowering interventions, and structural parameters associated with bleb function. Results From 131 patients randomised to bevacizumab (n=65) or placebo (n=66), 128 patients completed 12 months of follow-up (98%). At 12 months, success rates were higher in the bevacizumab group (complete success: 94% vs 83%; p=0.015; qualified success: 98% vs 90%; p=0.033). Within the placebo group, the requirement for topical therapy was higher at 6 months (p=0.045) and 12 months (p=0.045), and the requirement for bleb needling was higher at 1 month (p=0.035). Blebs within the bevacizumab group were larger at 1 month (p<0.001) and demonstrated less vessel inflammation (p<0.0001). Conclusion Bevacizumab given as a single intravitreal dose during trabeculectomy with MMC resulted in improved surgical success as 12 months. Furthermore, bevacizumab was associated with a significant reduction in the need for additional medication or further surgery to achieve target IOP. Bevacizumab was also associated with larger blebs that were less inflamed and required fewer subsequent interventions. Trial registration number ACTRN12614000375651.
cell therapies
2021-11-01 | Use of Amniotic Membrane in MMC-Augmented Trabeculectomy: A Retrospective Comparative Study
Purpose: Amniotic membrane transplantation (AMT) has shown promising results as an antifibrotic agent in trabeculectomy. We aimed to evaluate the additional effect of AMT in MMC-augmented trabeculectomy. Patients and Methods: This retrospective study analyzed the results of the first 12 postoperative months of glaucomatous eyes submitted to Moorfields Safer Surgery Trabeculectomy with MMC alone (non-AMT group) compared to MMC and AMT (AMT group). Both groups were compared in terms of intraocular pressure (IOP), number of antihypertensive medications and need for surgical reinterventions. Absolute and relative success rates 12 months after surgery were defined as IOP < 18 mmHg, without and with the use of antihypertensive medications, respectively. Results: The analysis included 51 eyes of 45 glaucoma patients (29 eyes in the non-AMT group and 22 in the AMT group). Mean IOP decreased from 24.72± 5.11 mmHg and 26.86± 10.62 mmHg preoperatively in non-AMT and AMT groups to 12.86± 4.22 mmHg and 12.60± 4.43 mmHg, respectively, at 12 months (p = 0.84). Postoperative number of medications decreased significantly in both groups. Absolute success was seen in 71% of non-AMT eyes and 55% of AMT eyes (p = 0.46), whereas relative success was obtained in 14% and 30%, respectively (p = 0.55). Reinterventions were needed in 28% of the eyes (11 bleb injection/needling and 4 Ahmed tube implantation) in the non-AMT group and in 27% of the AMT group (10 bleb injection/needling and 1 Ahmed tube implantation) (p = 0.89). Conclusion: Trabeculectomy combined with MMC and AMT did not show better results than trabeculectomy with MMC alone. Keywords: trabeculectomy, glaucoma, mitomycin C, amniotic membrane, antifibrotics, scarring
2021-03-09 | Is there a role for Amniotic Membrane as an antifibrotic agent in MMC-Augmented Trabeculectomy?
Abstract Purpose: Amniotic membrane transplantation (AMT) has shown promising results as an antifibrotic agent in trabeculectomy. We aimed to evaluate the additional effect of AMT in M MC-augmented trabeculectomy . Methods: This retrospective study analyzed the results of the first 12 postoperative months of glaucomatous eyes submitted to Moorfields Safer Surgery Trabeculectomy with MMC alone (non-AMT group) compared to MMC and AMT (AMT group). Both groups were compared in terms of intraocular pressure (IOP), number of antihypertensive medications and need for surgical reinterventions. Absolute and relative success rates 12 months after surgery were defined as IOP <18 mmHg, without and with the use of antihypertensive medications, respectively. Results: The analysis included 51 eyes of 45 glaucoma patients (29 eyes in the non-AMT group and 22 in the AMT group). Mean IOP decreased from 24,72±5,11 mmHg and 26,86±10,62 mmHg preoperatively in non-AMT and AMT groups to 12,86±4,22 mmHg and 12,60±4,43 mmHg, respectively, at 12 months (p=0,84). Postoperative number of medications decreased significantly in both groups. Absolute success was seen in 71% of non-AMT eyes and 55% of AMT eyes (p=0,46) whereas relative success was obtained in 14% and 30%, respectively (p=0,55). Reinterventions were needed in 28% of the eyes (11 bleb injection/needling and 4 Ahmed tube implantation) in the non-AMT group and in 27% of the AMT group (10 bleb injection/needling and 1 Ahmed tube implantation) (p=0,89). Conclusion: Trabeculectomy combined with MMC and AMT did not show better results than trabeculectomy with MMC alone.
2021-02-09 | Exploiting biomaterial approaches to manufacture an artificial trabecular meshwork: A progress report
Glaucoma is the second leading cause of irreversible blindness worldwide. Glaucoma is a progressive optic neuropathy in which permanent loss of peripheral vision results from neurodegeneration in the optic nerve head. The trabecular meshwork is responsible for regulating intraocular pressure, which to date, is the only modifiable risk factor associated with the development of glaucoma. Lowering intraocular pressure reduces glaucoma progression and current surgical approaches for glaucoma attempt to reduce outflow resistance through the trabecular meshwork. Many surgical approaches use minimally invasive glaucoma surgeries (MIGS) to control glaucoma. In this progress report, biomaterials currently employed to treat glaucoma, such as MIGS, and the issues associated with them are described. The report also discusses innovative biofabrication approaches that aim to revolutionise glaucoma treatment through tissue engineering and regenerative medicine (TERM). At present, there are very few applications targeted towards TM engineering in vivo, with a great proportion of these biomaterial structures being developed for in vitro model use. This is a consequence of the many anatomical and physiological attributes that must be considered when designing a TERM device for microscopic tissues, such as the trabecular meshwork. Ongoing advancements in TERM research from multi-disciplinary teams should lead to the development of a state-of-the-art device to restore trabecular meshwork function and provide a bio-engineering solution to improve patient outcomes.
2020-10-09 | Effectiveness and Safety of Trabeculectomy along with Amniotic Membrane Transplantation on Glaucoma: A Systematic Review
Purpose . To determine the effectiveness and safety of trabeculectomy along with amniotic membrane transplantation (AMT) for glaucoma. Methods . This systematic review was performed using RevMan 5.3. We searched PubMed, EMBASE, and the Cochrane Library and included studies published until September 2019. The treatment group included patients with AMT and trabeculectomy (group A), and the control group had only trabeculectomy (group B). We only included randomized controlled trials. The outcomes were intraocular pressure (IOP), complete success rate, number of antiglaucoma medications, and complications. Results . Five studies, including 174 eyes (87 eyes in the AMT group and 87 eyes in the control group), were eligible in this review. The parameters had no significant difference in heterogeneity between the AMT and control groups preoperatively. In the AMT group, the mean IOP was significantly lower at 3 and 12 months after operation (P < 0.0001 and P = 0.02, respectively), while the number of complete successes in the AMT group was significantly higher at 6 and 12 months (P = 0.02 and P = 0.003, respectively) compared with the control group. Complications, including a flat anterior chamber and hyphema, appeared to be decreased in the AMT group compared to the control group (P = 0.02 and P = 0.02, respectively). No differences were observed in the number of antiglaucoma medications, hypotony, encapsulated bleb, or choroidal detachment. Conclusion . Compared with only trabeculectomy, it is more efficient and safer to add AMT to trabeculectomy during glaucoma filtering surgery.
2019-04-01 | Use of Autologous Oral Mucosa Transplant to Treat Conjunctival Necrosis and Leakage after Trabeculectomy
Trabeculectomy is the most commonly performed filtration surgery. Although it is relatively easy to perform and effectively lowers intraocular pressure, it is not always without complications. To prevent scarring, mitomycin C is sometimes used as an adjunct, which can additionally lead to an increased incidence of ocular hypotony due to thinner and leaking blebs [1]. Treatment options for late-onset bleb leakage and overfiltration include a multitude of surgical and nonsurgical procedures.
oligonucleotides
2025-11-10 | Inhibition of chemokine MCP-1 with mNOX-E36 reduces scarring in a mouse model of glaucoma filtration surgery.
Monocyte-chemoattractant protein 1 (MCP-1), a potent recruiter of monocytes, is increased in tears of glaucoma patients with a greater propensity to scar. mNOX-E36 is a murine-specific analogue of NOX-E36, an anti-MCP-1 L-RNA aptamer that was previously shown to attenuate liver fibrosis in mice. Bleb scarring represents the biggest risk for failure of glaucoma filtration surgery (GFS), a procedure to reduce ocular pressure in glaucoma patients. Anti-fibrotic agents like mitomycin C (MMC) are used to prolong bleb longevity, albeit with significant cytotoxic effects. This study compared the efficacy of mNOX-E36 against MMC on post-operative fibrosis in a murine GFS model. GFS was performed on C57BL/6 mice, followed by subcutaneous or subconjunctival mNOX-E36 administration or MMC treatment. Conjunctival blebs were imaged on Day 1 and Day 7 post-GFS, corresponding to the inflammatory and fibrotic phases respectively. Blebs were harvested for immunofluorescence staining, multiplex cytokine analysis, Western blotting, and RT-qPCR analysis. The effect of mNOX-E36 on RAW264.7 macrophages and conjunctival fibroblasts was also investigated in vitro. Our results established that subconjunctival mNOX-E36 administration is more effective than subcutaneous mNOX-E36 injection in attenuating myeloid cell infiltration, pro-inflammatory cytokine expression, and fibrosis following GFS. Additionally, subconjunctival mNOX-E36 treatment exhibited comparable anti-fibrotic activity to MMC post-GFS. mNOX-E36 also inhibited both macrophage and conjunctival fibroblast activity. Our results thus demonstrate the efficacy of mNOX-E36 compared to clinical standard of care, MMC, in attenuating post-operative inflammation and fibrosis following GFS. NOX-E36 shows promise as an anti-fibrotic adjunctive treatment in GFS.
2023-10-18 | Effectiveness of conjunctival bleb scarring by knock-down of heat shock protein 47 in rat model
To evaluate the effectiveness of knock-down of heat shock protein 47 (HSP47) on conjunctival bleb scarring in a rat model and its possible mechanism.Male Sprague-Dawley rats were used for glaucoma filtration surgery (GFS) and were treated with either phosphate buffered solution, shControl, mitomycin C, or sh-HSP47 using a microsyringe immediately after GFS. The morphology of filtering blebs was observed postoperatively. The levels of HSP47 were analyzed at 2, 5, 8, and 11d after GFS via real-time quantitative polymerase chain reaction (PCR) and Western blot. The silencing effect of HSP47, the expression of collagen I and III, and the potential signaling pathways of HSP47 during scarification were explored 11d post GFS. The protein levels of transforming growth factor-β1 (TGF-β1), phospho-Smad2 (pSmad2), phospho-Smad3 (p-Smad3), and phospho-p38 (p-p38) were also analyzed using Western blot.Sh-HSP47 treatment significantly prolonged the functional filtration bleb retention. The levels of HSP47 were increased significantly at 5, 8, and 11d postoperatively compared to the control group (P<0.05, P<0.01, and P<0.001). The levels of HSP47 protein at day 11 postoperatively were significantly down-regulated after HSP47 silencing using sh-HSP47 adenovirus transfection (P<0.01). Expression levels of collagen I and III within the blebs were significantly reduced in the absence of HSP47 (P<0.01). Moreover, the protein levels of TGF-β1, p-Smad2/3, and p-p38 were dramatically inhibited after treatment with sh-HSP47 (P<0.01).The inhibitory effects of HSP47 knock-down on scarring after GFS have the potential to be an efficacious therapeutic option for the treatment of conjunctival bleb scarring.
2023-09-19 | Inhibition of heat shock protein 47 suppressed collagen production in Tenon’s capsule fibroblasts
Introduction. Glaucoma is the leading cause of irreversible blindness worldwide, and conjunctival bleb scarring remains the most frequent reason for the failure of glaucoma filtration surgery. Excessive proliferation of fibroblasts from Tenon’s capsule and excessive deposition of collagen contribute to the scarification of the conjunctival bleb. Heat shock protein 47 (HSP47) is assumed to act as a collagen-specific molecular chaperone, and thereby involved in the pathogenesis of fibrotic diseases. Therefore, we investigated the effect of HSP47 knockout against collagen type I (COLI) production in rat tenon’s fibroblasts. Material and methods. Newborn rat tenon’s fibroblasts were cultured and verified by anti-vimentin antibody. Transfection efficiency of small interference RNA targeted against HSP47 was confirmed by quantitative real-time polymerase chain reaction (RT-qPCR) at 48 h after siRNA transfection and by western blot at 72 h after transfection. The mRNA and protein expression of HSP 47 and COLI were detected by RT-qPCR and western blot. The proliferation of cells was measured by cell counting kit-8 assay. Results. HSP47 siRNA down-regulated the mRNA and protein levels of HSP47 in rat Tenon’s fibroblasts, and suppressed the mRNA and protein expression of COLI. Moreover, HSP47 siRNA had no significant effect on proliferation of rat Tenon’s fibroblasts. Conclusions. HSP47 siRNA inhibits the production of COLI in rat Tenon’s fibroblasts, and may be the potential therapeutic method in bleb scarring after glaucoma filtration surgery.
2023-04-20 | Emerging Evidence of Noncoding RNAs in Bleb Scarring after Glaucoma Filtration Surgery.
To conduct a narrative review of research articles on the potential anti- and pro-fibrotic mechanisms of noncoding RNAs following glaucoma filtration surgery. Keyword searches of PubMed, and Medline databases were conducted for articles discussing post-glaucoma filtration surgeries and noncoding RNA. Additional manual searches of reference lists of primary articles were performed. Fifteen primary research articles were identified. Four of the included papers used microarrays and qRT-PCR to identify up- or down-regulated microRNA (miRNA, miR) profiles and direct further study, with the remainder focusing on miRNAs or long noncoding RNAs (lncRNAs) based on previous work in other organs or disease processes. The results of the reviewed papers identified miR-26a, -29b, -139, -155, and -200a as having anti-fibrotic effects. In contrast, miRs-200b and -216b may play pro-fibrotic roles in filtration surgery fibrosis. lncRNAs including H19, NR003923, and 00028 have demonstrated pro-fibrotic effects. Noncoding RNAs including miRNAs and lncRNAs are emerging and promising therapeutic targets in the prevention of post-glaucoma filtration surgery fibrosis.
2021-08-02 | The TβR II-targeted aptamer S58 prevents fibrosis after glaucoma filtration surgery.
Glaucoma filtration surgery (GFS) is an effective clinical treatment for glaucoma when intraocular pressure (IOP) control is poor. However, the occurrence of conjunctival scarring at the surgical site is the main reason for failure of the surgery. In a previous study, we isolated and developed S58, a novel nucleic acid aptamer targeting TβR II, by systematic evolution of ligands by exponential enrichment (SELEX). Here, we show how S58 sterically inhibits the TβR II interaction with TGF-β. The effects of topical S58 treatment were studied in a rabbit model of GFS. At 6 postoperative weeks, S58 reduced fibrosis and prolonged bleb survival in rabbits after GFS. Further in vitro tests showed that the levels of fibrosis in S58 treated-Human Conjunctival Fibroblasts (HConFs) were decreased and that antioxidant defense was increased. In addition, the loss of nuclear factor erythroid 2-related factor 2 (Nrf2) or the inhibition of phosphoinositide 3-kinase/protein kinase B (PI3K/Akt) reversed the anti-fibrotic effects of S58. The present work suggests that S58 could effectively improve GFS surgical outcomes by activating the intracellular antioxidant defense PI3K/Akt/Nrf2 signaling pathway.
other
2026-02-02 | Pathology-responsive light-triggered conjunctival adhesive implantable hydrogels for effective anti-scarring after glaucoma filtering surgery.
Glaucoma filtration surgery (GFS) frequently fails due to uncontrolled subconjunctival scarring, driven by a cascade of postoperative inflammation, oxidative stress, and exaggerated myofibroblast activation. To address this, we developed an in-situ light-triggered hydrogel that enables strong conjunctival adhesion, bleb mechanical support, and pathology-responsive smart drug delivery for effective bleb scarring inhibition. The crosslinked hydrogel system prepared from functionalized carboxymethyl chitosan and epigallocatechin gallate (EGCG), prior to ultraviolet light (UV) exposure, was denoted as PNE hydrogel. After injection, PNE can adapt to ocular anatomy, and subsequent transconjunctival light exposure rapidly activates hydrogel crosslinking and covalent tissue adhesion, generating a mechanically robust hydrogel, denoted as PNE-UV hydrogel. Meanwhile, light-induced surface property changes further enhance conjunctival adhesion and reduce interface inflammatory cell infiltration. Concurrently, light-induced hydrophilic-to-hydrophobic hydrogel surface transition promotes water exclusion, further enhancing tissue adhesion to minimize interface inflammatory cell infiltration. With adequate mechanical strength, rapid self-healing, and good biosafety, PNE-UV provides essential mechanical bleb support during wound healing. Crucially, elevated postoperative reactive oxygen species (ROS) triggers intelligent EGCG release for over 17 days, which not only effectively scavenges ROS and promotes macrophage M1-to-M2 polarization to mitigate inflammation, but also suppresses TGF-β1-induced conjunctival fibroblast-to-myofibroblast transdifferentiation and myofibroblast proliferation. In a rabbit model of filtration surgery, PNE-UV hydrogel significantly prolonged bleb survival, reduced intraocular pressure, and decreased collagen deposition via mitigating oxidative stress and inflammation and suppressing fibrotic processes. Collectively, this interfacial adhesion and precise immunomodulation hydrogel presents an effective and clinically translatable strategy for post-GFS scarring prevention.
2024-02-07 | Comparing the safety and efficacy of intracameral tissue plasminogen activator (t-PA) in trabeculectomy with MMC Vs standard trabeculectomy with MMC only.
Objective: To find out the harmlessness and effectiveness of intra-cameral tissue plasminogen activator (t-PA) in trabeculectomy for patients with primary open angle glaucoma (POAG). Study Design: Quasi-experimental Trial. Setting: Eye B Department, of Khyber Teaching Hospital, Peshawar. Period: Jan. 2021 and Dec. 2021. Material & Methods: Patients with POAG, who were operated for trabeculectomy (trab.) Two groups were created out of study population i.e. Trab-MMC (Trab. With MMC done) and Trab-MMC/t-PA (Trab. With MMC + intra-cameral t-PA done). Success was defined as eyes having pressure (IOP) within the range of 8-20mmHg with at-least 25% reduction from pre-op IOP achieved with or without IOP lowering drugs. Results: Out of 20 participants (08 women and 12 men) 10 were allocated to each gp. Pre-op IOP was 28 ± 4.6 mmHg and 27 ± 4.8 mmHg, which dropped to 12.6 ± 3.8 mmHg and 11.1 ± 1.6 mmHg at 1st yr. post-op (p < 0.05) for both gps respectively. Surgical success was attained in 66% of Trab-MMC as compared to 86 % Trab-MMC/t-PA at 1st yr. (p = 0.44). Success with medication was 86 % compared to 100 % at 1st yr. respectively (p = 0.28). We didn’t observe any adverse effects with the use of intra-cameral t-PA. Conclusion: Adjunctive use of intra-cameral t-PA in trabeculectomy with MMC can result in improved outcome as compared to procedure without it. No side effects were noted with intra-cameral use of t-PA.
2023-05-22 | Plasma Rich in Growth Factors as an Adjuvant Agent in Non-Penetrating Deep Sclerectomy
The purpose of this study is to evaluate the utility and safety of plasma rich in growth factors immunosafe eye drops (is-ePRGF) in the postoperative treatment of non-penetrating deep sclerectomy (NPDS).This is a case-control study in patients with open-angle glaucoma. Group one (control) was not treated with is-ePRGF, while group two (is-ePRGF) was treated (four times a day for four months). Postoperative evaluations were performed at one day, one month, three months and six months. The main outcomes were: intraocular pressure (IOP), microcysts in blebs with AS-OCT and the number of hypotensive eye drops.Preoperatively, group one (n = 48 eyes) and group two (n = 47 eyes) were similar in age (71.5 ± 10.7 vs. 70.9 ± 10.0 years; p = 0.68), IOP (20.6 ± 10.2 vs. 23.0 ± 9.0 mmHg; p = 0.26) and number of hypotensive drugs (2.7 ± 0.8 vs. 2.8 ± 0.9; p = 0.40). The IOP at six months dropped to 15.0 ± 8.0 mmHg (IOP reduction: -27.2%) and 10.9 ± 4.3 mmHg (IOP reduction: -52.6%) for group one and group two, respectively (p < 0.01). At six months, blebs with microcysts were 62.5% (group one) and 76.7% (group two). Postoperative complications were observed in 12 eyes (25%) for group one and in 5 eyes (11%) for group two (p = 0.06). No specific complications related to the use of is-ePRGF were identified.Topical is-ePRGF seems to reduce IOP and the rate of complications in the medium term after NPDS, so it can be considered as a possible safe adjuvant to achieve surgical success.
2021-08-31 | Novel combination therapy reduces subconjunctival fibrosis after glaucoma filtration surgery in the rabbit model.
Glaucoma filtration surgery (GFS) is limited by subconjunctival, episcleral and scleral fibrosis sealing the trabeculectomy and scarring the filtering bleb. Mitomycin-C (MMC) is commonly applied intraoperatively to the subconjunctival and/or intrascleral space to reduce scarring and promotes GFS success but is associated with postoperative scleral melting and bleb leaks. IP-10 peptide (IP-10p), an ELR-negative CXC chemokine mimetic and inhibitor of fibroblast function, may be an alternative or adjunct to current postoperative GFS treatments. This study sought to determine if IP-10p produces histological changes in tissue remodelling, vascularity and fibrosis that enhance bleb survival after GFS. Rabbits underwent tube-assisted filtration surgery on the right eye with either: (a) IP-10p injected into bleb at time of surgery and postoperative days 2, 4 and 7, (b) intraoperative MMC or (c) intraoperative MMC plus IP-10p injected into bleb at time of surgery and postoperative days 2, 4 and 7. Left contralateral eyes were treated with balanced salt solution (BSS). IP-10p-treated blebs demonstrated reduced collagen deposition, cellularity and overall reduction of scar formation compared to BSS-control. Bleb vascularity was reduced compared to BSS-control and MMC treatment groups. Additionally, IP-10p/MMC treated eyes demonstrated an increased number of conjunctival goblet cells in bleb histology compared to the dramatic loss seen with MMC treatment alone. This study demonstrates that IP-10p significantly reduces histological scarring compared to BSS or MMC alone, does not damage the conjunctiva to the extent of current standards, and may be an alternative or adjunct to MMC for those undergoing GFS.
2018-08-01 | Matricellular Protein Levels in Aqueous Humor and Surgical Outcomes of Trabeculectomy
Purpose: The purpose of this study was to quantify levels of three matricellular proteins in the aqueous humor in patients with previous acute primary angle closure (APAC) and investigate their correlation with bleb morphology and surgical outcomes of trabeculectomy. Methods: In this prospective study, aqueous humor samples were collected from 40 previous APAC eyes. Concentrations of three matricellular proteins—secreted protein acidic and rich in cysteine (SPARC), thrombospondin-2, and osteopontin—were measured using multiplexed immunoassays kits. Intraocular pressure was measured using Goldmann application tonometry. Bleb morphology was assessed using anterior segment optical coherence tomography, and bleb score was calculated according to bleb size and reflectivity. Results: When previous APAC eyes were divided according to surgical outcome 18 months after trabeculectomy, SPARC protein was significantly higher in aqueous humor in the failure group (P = 0.009). When previous APAC eyes were divided according to SPARC level, eyes with low SPARC levels had significantly higher overall success rate compared with eyes with high SPARC levels (P = 0.005 for complete success and P = 0.018 for qualified success). Multiple logistic regression analyses showed that eyes with higher levels of SPARC were more likely to have a failed filtration surgery than were eyes with lower levels of SPARC. For complete success, P = 0.006 and odds ratio (OR) = 6.458; for qualified success, P = 0.033 and OR = 2.608. The level of SPARC was found to have a positive correlation with bleb score (P < 0.001, R2 = 0.471). Conclusions: In previous APAC patients, the SPARC level in aqueous humor is a prognostic factor for surgical results of trabeculectomy. Modulation of SPARC expression may have potential clinical applications after filtration surgery.
small molecules
2026-02-02 | STING deficiency alleviates scar formation after glaucoma filtration surgery by suppressing p38 MAPK-induced inflammation in mice.
Glaucoma filtration surgery (GFS) often fails because of excessive scar formation driven by inflammation and fibroblast activation. Although the stimulator of interferon genes (STING) pathway is involved in inflammatory responses, its role in post-surgical fibrosis remains unclear. A mouse GFS model was established in wild-type (WT) and STING-knockout (STING-KO) animals. A parallel cohort of WT mice received a single intraoperative subconjunctival injection of the STING inhibitor H151. Bleb survival, intraocular pressure, histopathology, collagen deposition, and inflammatory/fibrotic markers were evaluated for 28 days. RNA sequencing, Western blotting, and ELISA were employed to profile the p38/MAPK axis. Primary human Tenon's capsule fibroblasts were treated with angiotensin II in the presence or absence of STING silencing or H151 to corroborate mechanisms in vitro. STING expression was markedly up-regulated in fibroblasts within human and mice post-GFS tissues. STING-KO mice exhibited prolonged bleb survival together with reduced collagen deposition and fibroblast activation. RNA-sequencing revealed that STING deletion significantly altered the p38 mitogen-activated protein kinase (MAPK) pathway. Mechanistically, STING deficiency suppressed p38 MAPK phosphorylation, leading to decreased levels of the pro-inflammatory cytokines interleukin-6 (IL-6), tumor necrosis factor-α, IL-18, and IL-1β, as well as the fibrogenic factors α-SMA, collagen I, fibronectin, connective tissue growth factor, and collagen type III alpha 1 at the surgical sites. Consistently, the selective STING inhibitor H151 recapitulated these effects by suppressing p38 MAPK signaling and markedly reducing fibrotic scarring. STING deficiency alleviates scar formation after GFS by suppressing p38 MAPK pathway. Targeting STING/p38 axis may improve surgical outcomes by modulating the balance between inflammation and tissue repair.
2026-01-13 | Factors influencing the long-term-success of the XEN gel stent.
PURPOSE: The XEN gel stent is a minimally invasive surgical device for patients with open-angle glaucoma, developed to reduce complications associated with traditional filtration surgery. This study aimed to identify clinical factors that influence long-term surgical success, particularly in the context of postoperative conjunctival scarring. METHODS: In this retrospective study, 773 eyes of patients with glaucoma treated at a tertiary care center underwent implantation of the XEN gel stent. The primary outcome was long-term surgical success, defined as a reduction in intraocular pressure of at least 20% and achieving a target pressure of 18, 15, or 12 mmHg, either without (complete) or with (qualified) medication. Secondary outcomes included intraocular pressure reduction, change in best-corrected visual acuity and medication use. Potential risk factors were analysed using Kaplan-Meier survival curves and multivariable Cox regression. RESULTS: At 24 months, complete and qualified success for a target pressure of 18 mmHg was achieved in 50% and 64% of cases, respectively; at 72 months, in 35% and 54%. Visual acuity remained stable. Female sex, mitomycin C dose, moderately elevated baseline pressure, and lower pressure on the first postoperative day were associated with significantly higher success rates (p < 0.05). Glaucoma subtype and previous incisional glaucoma surgery had no significant effect. CONCLUSION: Sex, lower antimetabolite dose and intraocular pressure values before and shortly after surgery are significant predictors of long-term success following XEN gel stent implantation.
2025-08-29 | A Suturable and Drug-Free Polyzwitterionic Hydrogel for Alleviating Scar Formation After Glaucoma Filtration Surgery.
Glaucoma stands as a leading cause of irreversible blindness worldwide. Glaucoma filtration surgery (GFS) is the main surgical approach for its treatment. However, postoperative inflammation or immune responses can stimulate excessive scar formation, compromising surgical outcomes and potentially leading to complications such as uncontrolled intraocular pressure (IOP). This study aimed to develop a suturable polyzwitterionic hydrogel by combining 2-((2-hydroxy-3-(methacryloyloxy) propyl) dimethyl ammonio) acetate (CBOH), a zwitterionic monomer containing hydroxyl groups, with 2-hydroxyethyl methacrylate (HEMA) to prevent GFS-induced scar formation. The introduction of the CBOH component imparts excellent antifouling properties and a relatively low modulus, giving it mechanical characteristics similar to native ocular tissue. This facilitates the prevention of scar tissue formation following GFS and reduces foreign body sensation caused by long-term implant materials. In an animal model of GFS, P(HEMA-CBOH) hydrogel maintained filtration bleb survival and lowered IOP for up to 4 weeks postoperatively. Furturemore, it reduced collagen deposition and α-SMA expression within conjunctival and scleral tissue, demonstrating their efficacy in inhibiting scar formation and improving GFS outcomes. Overall, as a suturable, drug-free polyzwitterionic hydrogel, P(HEMA-CBOH) holds significant potential for clinical applications in GFS, largely due to its inherent antifouling properties.
2025-07-16 | Inhibitory Effects of 3',4'-Dihydroxyflavonol in a Rabbit Model of Minimally Invasive Bleb Surgery With PreserFlo MicroShunt.
The success of minimally invasive bleb surgery (MIBS) such as the PreserFlo MicroShunt (PFMS) is limited by post-operative bleb fibrosis. Current clinical practice prescribes the use of off-label cytotoxic antimetabolites such as Mitomycin C (MMC) as antifibrotic therapy. This study investigates the anti-scarring properties of a novel compound, 3',4'-Dihydroxyflavonol (DiOHF) in a rabbit model of PFMS filtration surgery. Fifteen New Zealand white rabbits underwent unilateral MIBS with PFMS. Treatment was randomised to the following groups: (1) vehicle (n = 5), (2) DiOHF (n = 5), both applied three times daily for 2 weeks or (3) a single dose of MMC administered intraoperatively (n = 5). Blebs were photographed post-operatively on Days 0, 7 and 14 for clinical examination. Eyes were harvested on Day 14 and processed for immunohistochemical tissue staining to assess collagen deposition, expression of αSMA, oxidative stress, fibroblast activity, angiogenesis and inflammation in the conjunctiva/Tenon's layer. At 2-weeks post-surgery, MMC blebs were larger and more ischaemic than other treatments (Bleb size: MMC vs. DiOHF, p = 0.0098; MMC vs. vehicle, p = 0.0001. Ischaemia: p = 0.0004 for both). Compared to vehicle control, DiOHF blebs expressed decreased vimentin (p = 0.0099), αSMA (p = 0.0231) and 3-nitrotyrosine (p = 0.0410) after 2 weeks. DiOHF blebs expressed less CD45 than other treatments (DiOHF vs. Vehicle, p = 0.0013; DiOHF vs. MMC, p = 0.0232) and less collagen accumulation (DiOHF vs. vehicle, p = 0.0512). There was no difference in CD31 expression between treatment groups. DiOHF inhibited scarring following implantation of PFMS in rabbit eyes by reducing local oxidative stress, inflammation and fibroblastic activity. DiOHF may be a safer and more effective wound modulating agent than the conventional use of MMC.
2024-10-16 | 3',4'-Dihydroxyflavonol Inhibits Fibrotic Response in a Rabbit Model of Glaucoma Filtration Surgery.
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.
antibodies
2024-12-02 | Targeting CCL5 Attenuates Fibrosis via Activation of PI3k/Akt Signaling Axis After Glaucoma Filtration Surgery.
Glaucoma filtration surgery (GFS) stands as a paramount clinical intervention for glaucoma. Nonetheless, the prevalent cause of GFS failure is filtration bleb scarring, and the role of inflammation and immune response in contributing to fibrosis remains elusive. The study employed 30 female Sprague-Dawley rats (8 weeks old, 200-250 g) to assess the anti-scarring impact of the Chemokine (C-C motif) receptor 5 (CCR5)-Chemokine (C-C motif) ligand 5 (CCL5) antibody after GFS. Additionally, anti-fibrotic effects on HConFs were examined, creating an intra-operative inflammatory response using damaged-HConFs supernatant medium (DHSM). In vitro and in vivo validation aimed to elucidate the potential anti-fibrotic molecular mechanism of the CCR5-CCL5 antibody. The CCR5-CCL5 antibody effectively prolonged filtration bleb duration and enhanced the functionality of the filtered bleb. Improved postoperative intraocular pressure values (IOP) and morphological images were observed in the CCR5-CCL5 antibody-treated group. Histochemical staining and cellular experiments confirmed the antifibrotic function of the CCR5-CCL5 antibody. Notably, M2-type macrophage polarization was reduced in the CCR5-CCL5 antibody-treated model. CCL5-induced fibrosis in HConFs was mediated through the PI3K/Akt signaling pathway. Consistently, inhibition of PI3K/Akt significantly attenuated the profibrotic effects of CCR5-CCL5. Mechanistically, the CCL5 antibody exerts its antifibrotic effect by targeting CCR5 on HConFs, leading to the inhibition of the PI3K/Akt mechanism. This study unveils that CCR5-CCL5 promotes fibrosis in GFS through inflammatory stimulation of HConFs and enhanced activation of the PI3K/Akt signaling pathway. The findings suggest that intraoperative CCR5-CCL5 antibody treatment could serve as a cost-effective therapeutic agent or a useful adjuvant in preventing ocular bleb scar formation.
2024-10-26 | Conjunctival Advancement Procedure for Repairing Conjunctival Exposure of the PreserFlo MicroShunt
A 59-year-old Japanese woman with primary open-angle glaucoma underwent PreserFlo MicroShunt (PFM) (Santen Pharmaceutical Co., Ltd., Osaka, Japan) implantation in her left eye. Six weeks postoperatively, a conjunctival exposure of the posterior end of the device was observed, accompanied by aqueous leakage. The patient had no identifiable risk factors for exposure, such as previous conjunctival incisional surgeries, significant blepharitis, or needling procedures. Conjunctival advancement surgery was performed to cover the exposed device. After the sufficient dissection of scar tissue surrounding the PFM and the reapproximation of the conjunctiva, the device was successfully covered. Postoperatively, the filtration bleb remained formed, and the intraocular pressure (IOP) was controlled. No recurrence of device exposure was observed after 18 months of follow-up. Although PFM device exposure is a rare complication, it requires prompt surgical intervention to prevent infection and maintain IOP control. Conjunctival advancement surgery is an effective treatment option that allows for the repair of the exposure while preserving the filtration function of the device.
2024-03-01 | Evaluation of The Efficacy of Aflibercept versus Mitomycin C in Trabeculectomy in Cases of Primary Open Angle Glaucoma
Background: Post-operative scarring at the bleb site is a major factor in whether or not a trabeculectomy is successful. Mitomycin C and anti-vascular endothelial growth factor drugs like Aflibercept have been frequently used as supplementary treatments to trabeculectomy.Aim of the Study: This study aims to compare the efficacy of aflibercept and mitomycin c in trabeculectomy in patients with primary open-angle glaucoma.Patients and Methods: This prospective interventional study was carried out in Al-Azhar University Hospital in New Damietta from 2021 to 2023 on 40 patients with uncontrollable bilateral primary open angle glaucoma. Patients were divided into 2 groups each patient was represented in each group with one eye: Group 1, Included 20 eyes with medically uncontrolled primary open-angle glaucoma in which sub scleral trabeculectomy with intraoperative mitomycin C [0.3mg/1ml] topical application was done. Group 2, Included 20 eyes with medically uncontrolled primary open-angle glaucoma in which subscleral trabeculectomy with intraoperative subconjunctival single dose of Eylea [2 mg / 0.05 mL] was done.Results: According to the IOP, we found a statistically significant reduction in the IOP from 25 [23-28] mmHg in group 1 and 25 [23-28] mmHg in group 2 at the baseline to 14 [13-15] mmHg in group 1 and 16 [15-16] mmHg in group 2 at 12 months postoperative [P = 0.001]. In terms of the Bleb evaluation, the Mainz score was used for the Bleb assessment all over the follow-up periods. It consists of seven main domains, bleb height, peripheral vascularity, central vascularity, transparency, microcyst formation, and conjunctival mobility. We found no statistically significant difference between the 2 groups as regards all Mainz domains over the follow-up periods [P > 0.05 for all].Conclusion: The use of intraoperative subconjunctival single-dose Aflibercept in trabeculectomy is safe effective and comparable to the use of MMC in terms of the advantage of avoiding the potentially dangerous complications related to MMC use.
2023-09-04 | Treatment of filtration bleb dysfunction after glaucoma surgery by needle revision of filtration bleb combined with conbercept.
Filtration surgery (Trabeculectomy) is the main treatment for glaucoma. The scarring of the filtration bleb and obstruction of the outflow of aqueous humor through the filtration channel are the main reasons of the surgery failure. The objective of this study was to determine the clinical efficacy of needle revision of filtration blebs combined with subconjunctival injection of conbercept on the functional bleb formation in glaucoma patients with eye pressure out of control after trabeculectomy. A total of 48 eyes with poor filtration bleb function after trabeculectomy for glaucoma were treated with needle revision of filtration bleb combined with subconjunctival injection of conbercept. After the treatment, the patients were followed up for 3 months during which visual acuity, intraocular pressure, slit lamp and ultrasound biomicroscope examinations were performed. Intraoperative and postoperative complications were recorded. The visual acuity and intraocular pressure were significantly improved after the needle revision of filtration blebs. Among the 48 eyes, 39 eyes still had functional blebs at the end of the follow-up period, and filtration blebs failed in 9 eyes 2 to 8 weeks after the removal of the needle. The survival rate of filtration blebs at 3 months after needle revision was (79.06 ± 3.42%), and 81.25% (39/48) of the eyes showed good formation rate of functional bleb at the last follow-up. Three months after needle revision, there was local scar formation in some filtration blebs. Part of the filtration blebs showed mild thickening of the local subconjunctival tissue, and the filtration bleb was slightly raised and diffuse, showing a multi-cavity and thin-walled shape in some blebs. Ultrasound biomicroscopy examination showed relative structural manifestations. Subconjunctival hemorrhage occurred in 43 patients during and after the operation. Low intraocular pressure occurred in 8 patients with the lowest pressure of 5 mm Hg. Choroidal edema was observed in 3 patients. Five patients had intraoperative conjunctival hemorrhage in the anterior chamber, and hyphema occurred. All complications were self-limited and resolved without surgical intervention. Needle revision of filtration bleb combined with anti-VEGF drugs is a safe and effective method for the treatment of filtration bleb dysfunction after surgery of glaucoma.
2023-08-04 | Intravitreal bevacizumab improves trabeculectomy survival at 12 months: the bevacizumab in trabeculectomy study—a randomised clinical trial
Aims To evaluate the effect of an intraoperative dose of intravitreal bevacizumab (Avastin) on surgical success following trabeculectomy with mitomycin-C (MMC) over 12 months. Methods A single centre, parallel, double-blinded randomised, placebo-controlled trial recruiting patients requiring trabeculectomy for progressing glaucoma. Patients were randomised to intravitreal bevacizumab or placebo. Main outcome measure The primary outcome of treatment success was defined by ‘complete success’ when intraocular pressure (IOP) remained less than a predefined target IOP without the requirement of topical medication, or ‘qualified success’ where topical medication was required to meet the predefined target IOP threshold. Secondary outcomes included the need for subsequent IOP-lowering interventions, and structural parameters associated with bleb function. Results From 131 patients randomised to bevacizumab (n=65) or placebo (n=66), 128 patients completed 12 months of follow-up (98%). At 12 months, success rates were higher in the bevacizumab group (complete success: 94% vs 83%; p=0.015; qualified success: 98% vs 90%; p=0.033). Within the placebo group, the requirement for topical therapy was higher at 6 months (p=0.045) and 12 months (p=0.045), and the requirement for bleb needling was higher at 1 month (p=0.035). Blebs within the bevacizumab group were larger at 1 month (p<0.001) and demonstrated less vessel inflammation (p<0.0001). Conclusion Bevacizumab given as a single intravitreal dose during trabeculectomy with MMC resulted in improved surgical success as 12 months. Furthermore, bevacizumab was associated with a significant reduction in the need for additional medication or further surgery to achieve target IOP. Bevacizumab was also associated with larger blebs that were less inflamed and required fewer subsequent interventions. Trial registration number ACTRN12614000375651.
cell therapies
2021-11-01 | Use of Amniotic Membrane in MMC-Augmented Trabeculectomy: A Retrospective Comparative Study
Purpose: Amniotic membrane transplantation (AMT) has shown promising results as an antifibrotic agent in trabeculectomy. We aimed to evaluate the additional effect of AMT in MMC-augmented trabeculectomy. Patients and Methods: This retrospective study analyzed the results of the first 12 postoperative months of glaucomatous eyes submitted to Moorfields Safer Surgery Trabeculectomy with MMC alone (non-AMT group) compared to MMC and AMT (AMT group). Both groups were compared in terms of intraocular pressure (IOP), number of antihypertensive medications and need for surgical reinterventions. Absolute and relative success rates 12 months after surgery were defined as IOP < 18 mmHg, without and with the use of antihypertensive medications, respectively. Results: The analysis included 51 eyes of 45 glaucoma patients (29 eyes in the non-AMT group and 22 in the AMT group). Mean IOP decreased from 24.72± 5.11 mmHg and 26.86± 10.62 mmHg preoperatively in non-AMT and AMT groups to 12.86± 4.22 mmHg and 12.60± 4.43 mmHg, respectively, at 12 months (p = 0.84). Postoperative number of medications decreased significantly in both groups. Absolute success was seen in 71% of non-AMT eyes and 55% of AMT eyes (p = 0.46), whereas relative success was obtained in 14% and 30%, respectively (p = 0.55). Reinterventions were needed in 28% of the eyes (11 bleb injection/needling and 4 Ahmed tube implantation) in the non-AMT group and in 27% of the AMT group (10 bleb injection/needling and 1 Ahmed tube implantation) (p = 0.89). Conclusion: Trabeculectomy combined with MMC and AMT did not show better results than trabeculectomy with MMC alone. Keywords: trabeculectomy, glaucoma, mitomycin C, amniotic membrane, antifibrotics, scarring
2021-03-09 | Is there a role for Amniotic Membrane as an antifibrotic agent in MMC-Augmented Trabeculectomy?
Abstract Purpose: Amniotic membrane transplantation (AMT) has shown promising results as an antifibrotic agent in trabeculectomy. We aimed to evaluate the additional effect of AMT in M MC-augmented trabeculectomy . Methods: This retrospective study analyzed the results of the first 12 postoperative months of glaucomatous eyes submitted to Moorfields Safer Surgery Trabeculectomy with MMC alone (non-AMT group) compared to MMC and AMT (AMT group). Both groups were compared in terms of intraocular pressure (IOP), number of antihypertensive medications and need for surgical reinterventions. Absolute and relative success rates 12 months after surgery were defined as IOP <18 mmHg, without and with the use of antihypertensive medications, respectively. Results: The analysis included 51 eyes of 45 glaucoma patients (29 eyes in the non-AMT group and 22 in the AMT group). Mean IOP decreased from 24,72±5,11 mmHg and 26,86±10,62 mmHg preoperatively in non-AMT and AMT groups to 12,86±4,22 mmHg and 12,60±4,43 mmHg, respectively, at 12 months (p=0,84). Postoperative number of medications decreased significantly in both groups. Absolute success was seen in 71% of non-AMT eyes and 55% of AMT eyes (p=0,46) whereas relative success was obtained in 14% and 30%, respectively (p=0,55). Reinterventions were needed in 28% of the eyes (11 bleb injection/needling and 4 Ahmed tube implantation) in the non-AMT group and in 27% of the AMT group (10 bleb injection/needling and 1 Ahmed tube implantation) (p=0,89). Conclusion: Trabeculectomy combined with MMC and AMT did not show better results than trabeculectomy with MMC alone.
2021-02-09 | Exploiting biomaterial approaches to manufacture an artificial trabecular meshwork: A progress report
Glaucoma is the second leading cause of irreversible blindness worldwide. Glaucoma is a progressive optic neuropathy in which permanent loss of peripheral vision results from neurodegeneration in the optic nerve head. The trabecular meshwork is responsible for regulating intraocular pressure, which to date, is the only modifiable risk factor associated with the development of glaucoma. Lowering intraocular pressure reduces glaucoma progression and current surgical approaches for glaucoma attempt to reduce outflow resistance through the trabecular meshwork. Many surgical approaches use minimally invasive glaucoma surgeries (MIGS) to control glaucoma. In this progress report, biomaterials currently employed to treat glaucoma, such as MIGS, and the issues associated with them are described. The report also discusses innovative biofabrication approaches that aim to revolutionise glaucoma treatment through tissue engineering and regenerative medicine (TERM). At present, there are very few applications targeted towards TM engineering in vivo, with a great proportion of these biomaterial structures being developed for in vitro model use. This is a consequence of the many anatomical and physiological attributes that must be considered when designing a TERM device for microscopic tissues, such as the trabecular meshwork. Ongoing advancements in TERM research from multi-disciplinary teams should lead to the development of a state-of-the-art device to restore trabecular meshwork function and provide a bio-engineering solution to improve patient outcomes.
2020-10-09 | Effectiveness and Safety of Trabeculectomy along with Amniotic Membrane Transplantation on Glaucoma: A Systematic Review
Purpose . To determine the effectiveness and safety of trabeculectomy along with amniotic membrane transplantation (AMT) for glaucoma. Methods . This systematic review was performed using RevMan 5.3. We searched PubMed, EMBASE, and the Cochrane Library and included studies published until September 2019. The treatment group included patients with AMT and trabeculectomy (group A), and the control group had only trabeculectomy (group B). We only included randomized controlled trials. The outcomes were intraocular pressure (IOP), complete success rate, number of antiglaucoma medications, and complications. Results . Five studies, including 174 eyes (87 eyes in the AMT group and 87 eyes in the control group), were eligible in this review. The parameters had no significant difference in heterogeneity between the AMT and control groups preoperatively. In the AMT group, the mean IOP was significantly lower at 3 and 12 months after operation (P < 0.0001 and P = 0.02, respectively), while the number of complete successes in the AMT group was significantly higher at 6 and 12 months (P = 0.02 and P = 0.003, respectively) compared with the control group. Complications, including a flat anterior chamber and hyphema, appeared to be decreased in the AMT group compared to the control group (P = 0.02 and P = 0.02, respectively). No differences were observed in the number of antiglaucoma medications, hypotony, encapsulated bleb, or choroidal detachment. Conclusion . Compared with only trabeculectomy, it is more efficient and safer to add AMT to trabeculectomy during glaucoma filtering surgery.
2019-04-01 | Use of Autologous Oral Mucosa Transplant to Treat Conjunctival Necrosis and Leakage after Trabeculectomy
Trabeculectomy is the most commonly performed filtration surgery. Although it is relatively easy to perform and effectively lowers intraocular pressure, it is not always without complications. To prevent scarring, mitomycin C is sometimes used as an adjunct, which can additionally lead to an increased incidence of ocular hypotony due to thinner and leaking blebs [1]. Treatment options for late-onset bleb leakage and overfiltration include a multitude of surgical and nonsurgical procedures.
oligonucleotides
2025-11-10 | Inhibition of chemokine MCP-1 with mNOX-E36 reduces scarring in a mouse model of glaucoma filtration surgery.
Monocyte-chemoattractant protein 1 (MCP-1), a potent recruiter of monocytes, is increased in tears of glaucoma patients with a greater propensity to scar. mNOX-E36 is a murine-specific analogue of NOX-E36, an anti-MCP-1 L-RNA aptamer that was previously shown to attenuate liver fibrosis in mice. Bleb scarring represents the biggest risk for failure of glaucoma filtration surgery (GFS), a procedure to reduce ocular pressure in glaucoma patients. Anti-fibrotic agents like mitomycin C (MMC) are used to prolong bleb longevity, albeit with significant cytotoxic effects. This study compared the efficacy of mNOX-E36 against MMC on post-operative fibrosis in a murine GFS model. GFS was performed on C57BL/6 mice, followed by subcutaneous or subconjunctival mNOX-E36 administration or MMC treatment. Conjunctival blebs were imaged on Day 1 and Day 7 post-GFS, corresponding to the inflammatory and fibrotic phases respectively. Blebs were harvested for immunofluorescence staining, multiplex cytokine analysis, Western blotting, and RT-qPCR analysis. The effect of mNOX-E36 on RAW264.7 macrophages and conjunctival fibroblasts was also investigated in vitro. Our results established that subconjunctival mNOX-E36 administration is more effective than subcutaneous mNOX-E36 injection in attenuating myeloid cell infiltration, pro-inflammatory cytokine expression, and fibrosis following GFS. Additionally, subconjunctival mNOX-E36 treatment exhibited comparable anti-fibrotic activity to MMC post-GFS. mNOX-E36 also inhibited both macrophage and conjunctival fibroblast activity. Our results thus demonstrate the efficacy of mNOX-E36 compared to clinical standard of care, MMC, in attenuating post-operative inflammation and fibrosis following GFS. NOX-E36 shows promise as an anti-fibrotic adjunctive treatment in GFS.
2023-10-18 | Effectiveness of conjunctival bleb scarring by knock-down of heat shock protein 47 in rat model
To evaluate the effectiveness of knock-down of heat shock protein 47 (HSP47) on conjunctival bleb scarring in a rat model and its possible mechanism.Male Sprague-Dawley rats were used for glaucoma filtration surgery (GFS) and were treated with either phosphate buffered solution, shControl, mitomycin C, or sh-HSP47 using a microsyringe immediately after GFS. The morphology of filtering blebs was observed postoperatively. The levels of HSP47 were analyzed at 2, 5, 8, and 11d after GFS via real-time quantitative polymerase chain reaction (PCR) and Western blot. The silencing effect of HSP47, the expression of collagen I and III, and the potential signaling pathways of HSP47 during scarification were explored 11d post GFS. The protein levels of transforming growth factor-β1 (TGF-β1), phospho-Smad2 (pSmad2), phospho-Smad3 (p-Smad3), and phospho-p38 (p-p38) were also analyzed using Western blot.Sh-HSP47 treatment significantly prolonged the functional filtration bleb retention. The levels of HSP47 were increased significantly at 5, 8, and 11d postoperatively compared to the control group (P<0.05, P<0.01, and P<0.001). The levels of HSP47 protein at day 11 postoperatively were significantly down-regulated after HSP47 silencing using sh-HSP47 adenovirus transfection (P<0.01). Expression levels of collagen I and III within the blebs were significantly reduced in the absence of HSP47 (P<0.01). Moreover, the protein levels of TGF-β1, p-Smad2/3, and p-p38 were dramatically inhibited after treatment with sh-HSP47 (P<0.01).The inhibitory effects of HSP47 knock-down on scarring after GFS have the potential to be an efficacious therapeutic option for the treatment of conjunctival bleb scarring.
2023-09-19 | Inhibition of heat shock protein 47 suppressed collagen production in Tenon’s capsule fibroblasts
Introduction. Glaucoma is the leading cause of irreversible blindness worldwide, and conjunctival bleb scarring remains the most frequent reason for the failure of glaucoma filtration surgery. Excessive proliferation of fibroblasts from Tenon’s capsule and excessive deposition of collagen contribute to the scarification of the conjunctival bleb. Heat shock protein 47 (HSP47) is assumed to act as a collagen-specific molecular chaperone, and thereby involved in the pathogenesis of fibrotic diseases. Therefore, we investigated the effect of HSP47 knockout against collagen type I (COLI) production in rat tenon’s fibroblasts. Material and methods. Newborn rat tenon’s fibroblasts were cultured and verified by anti-vimentin antibody. Transfection efficiency of small interference RNA targeted against HSP47 was confirmed by quantitative real-time polymerase chain reaction (RT-qPCR) at 48 h after siRNA transfection and by western blot at 72 h after transfection. The mRNA and protein expression of HSP 47 and COLI were detected by RT-qPCR and western blot. The proliferation of cells was measured by cell counting kit-8 assay. Results. HSP47 siRNA down-regulated the mRNA and protein levels of HSP47 in rat Tenon’s fibroblasts, and suppressed the mRNA and protein expression of COLI. Moreover, HSP47 siRNA had no significant effect on proliferation of rat Tenon’s fibroblasts. Conclusions. HSP47 siRNA inhibits the production of COLI in rat Tenon’s fibroblasts, and may be the potential therapeutic method in bleb scarring after glaucoma filtration surgery.
2023-04-20 | Emerging Evidence of Noncoding RNAs in Bleb Scarring after Glaucoma Filtration Surgery.
To conduct a narrative review of research articles on the potential anti- and pro-fibrotic mechanisms of noncoding RNAs following glaucoma filtration surgery. Keyword searches of PubMed, and Medline databases were conducted for articles discussing post-glaucoma filtration surgeries and noncoding RNA. Additional manual searches of reference lists of primary articles were performed. Fifteen primary research articles were identified. Four of the included papers used microarrays and qRT-PCR to identify up- or down-regulated microRNA (miRNA, miR) profiles and direct further study, with the remainder focusing on miRNAs or long noncoding RNAs (lncRNAs) based on previous work in other organs or disease processes. The results of the reviewed papers identified miR-26a, -29b, -139, -155, and -200a as having anti-fibrotic effects. In contrast, miRs-200b and -216b may play pro-fibrotic roles in filtration surgery fibrosis. lncRNAs including H19, NR003923, and 00028 have demonstrated pro-fibrotic effects. Noncoding RNAs including miRNAs and lncRNAs are emerging and promising therapeutic targets in the prevention of post-glaucoma filtration surgery fibrosis.
2021-08-02 | The TβR II-targeted aptamer S58 prevents fibrosis after glaucoma filtration surgery.
Glaucoma filtration surgery (GFS) is an effective clinical treatment for glaucoma when intraocular pressure (IOP) control is poor. However, the occurrence of conjunctival scarring at the surgical site is the main reason for failure of the surgery. In a previous study, we isolated and developed S58, a novel nucleic acid aptamer targeting TβR II, by systematic evolution of ligands by exponential enrichment (SELEX). Here, we show how S58 sterically inhibits the TβR II interaction with TGF-β. The effects of topical S58 treatment were studied in a rabbit model of GFS. At 6 postoperative weeks, S58 reduced fibrosis and prolonged bleb survival in rabbits after GFS. Further in vitro tests showed that the levels of fibrosis in S58 treated-Human Conjunctival Fibroblasts (HConFs) were decreased and that antioxidant defense was increased. In addition, the loss of nuclear factor erythroid 2-related factor 2 (Nrf2) or the inhibition of phosphoinositide 3-kinase/protein kinase B (PI3K/Akt) reversed the anti-fibrotic effects of S58. The present work suggests that S58 could effectively improve GFS surgical outcomes by activating the intracellular antioxidant defense PI3K/Akt/Nrf2 signaling pathway.
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2026-02-02 | Pathology-responsive light-triggered conjunctival adhesive implantable hydrogels for effective anti-scarring after glaucoma filtering surgery.
Glaucoma filtration surgery (GFS) frequently fails due to uncontrolled subconjunctival scarring, driven by a cascade of postoperative inflammation, oxidative stress, and exaggerated myofibroblast activation. To address this, we developed an in-situ light-triggered hydrogel that enables strong conjunctival adhesion, bleb mechanical support, and pathology-responsive smart drug delivery for effective bleb scarring inhibition. The crosslinked hydrogel system prepared from functionalized carboxymethyl chitosan and epigallocatechin gallate (EGCG), prior to ultraviolet light (UV) exposure, was denoted as PNE hydrogel. After injection, PNE can adapt to ocular anatomy, and subsequent transconjunctival light exposure rapidly activates hydrogel crosslinking and covalent tissue adhesion, generating a mechanically robust hydrogel, denoted as PNE-UV hydrogel. Meanwhile, light-induced surface property changes further enhance conjunctival adhesion and reduce interface inflammatory cell infiltration. Concurrently, light-induced hydrophilic-to-hydrophobic hydrogel surface transition promotes water exclusion, further enhancing tissue adhesion to minimize interface inflammatory cell infiltration. With adequate mechanical strength, rapid self-healing, and good biosafety, PNE-UV provides essential mechanical bleb support during wound healing. Crucially, elevated postoperative reactive oxygen species (ROS) triggers intelligent EGCG release for over 17 days, which not only effectively scavenges ROS and promotes macrophage M1-to-M2 polarization to mitigate inflammation, but also suppresses TGF-β1-induced conjunctival fibroblast-to-myofibroblast transdifferentiation and myofibroblast proliferation. In a rabbit model of filtration surgery, PNE-UV hydrogel significantly prolonged bleb survival, reduced intraocular pressure, and decreased collagen deposition via mitigating oxidative stress and inflammation and suppressing fibrotic processes. Collectively, this interfacial adhesion and precise immunomodulation hydrogel presents an effective and clinically translatable strategy for post-GFS scarring prevention.
2024-02-07 | Comparing the safety and efficacy of intracameral tissue plasminogen activator (t-PA) in trabeculectomy with MMC Vs standard trabeculectomy with MMC only.
Objective: To find out the harmlessness and effectiveness of intra-cameral tissue plasminogen activator (t-PA) in trabeculectomy for patients with primary open angle glaucoma (POAG). Study Design: Quasi-experimental Trial. Setting: Eye B Department, of Khyber Teaching Hospital, Peshawar. Period: Jan. 2021 and Dec. 2021. Material & Methods: Patients with POAG, who were operated for trabeculectomy (trab.) Two groups were created out of study population i.e. Trab-MMC (Trab. With MMC done) and Trab-MMC/t-PA (Trab. With MMC + intra-cameral t-PA done). Success was defined as eyes having pressure (IOP) within the range of 8-20mmHg with at-least 25% reduction from pre-op IOP achieved with or without IOP lowering drugs. Results: Out of 20 participants (08 women and 12 men) 10 were allocated to each gp. Pre-op IOP was 28 ± 4.6 mmHg and 27 ± 4.8 mmHg, which dropped to 12.6 ± 3.8 mmHg and 11.1 ± 1.6 mmHg at 1st yr. post-op (p < 0.05) for both gps respectively. Surgical success was attained in 66% of Trab-MMC as compared to 86 % Trab-MMC/t-PA at 1st yr. (p = 0.44). Success with medication was 86 % compared to 100 % at 1st yr. respectively (p = 0.28). We didn’t observe any adverse effects with the use of intra-cameral t-PA. Conclusion: Adjunctive use of intra-cameral t-PA in trabeculectomy with MMC can result in improved outcome as compared to procedure without it. No side effects were noted with intra-cameral use of t-PA.
2023-05-22 | Plasma Rich in Growth Factors as an Adjuvant Agent in Non-Penetrating Deep Sclerectomy
The purpose of this study is to evaluate the utility and safety of plasma rich in growth factors immunosafe eye drops (is-ePRGF) in the postoperative treatment of non-penetrating deep sclerectomy (NPDS).This is a case-control study in patients with open-angle glaucoma. Group one (control) was not treated with is-ePRGF, while group two (is-ePRGF) was treated (four times a day for four months). Postoperative evaluations were performed at one day, one month, three months and six months. The main outcomes were: intraocular pressure (IOP), microcysts in blebs with AS-OCT and the number of hypotensive eye drops.Preoperatively, group one (n = 48 eyes) and group two (n = 47 eyes) were similar in age (71.5 ± 10.7 vs. 70.9 ± 10.0 years; p = 0.68), IOP (20.6 ± 10.2 vs. 23.0 ± 9.0 mmHg; p = 0.26) and number of hypotensive drugs (2.7 ± 0.8 vs. 2.8 ± 0.9; p = 0.40). The IOP at six months dropped to 15.0 ± 8.0 mmHg (IOP reduction: -27.2%) and 10.9 ± 4.3 mmHg (IOP reduction: -52.6%) for group one and group two, respectively (p < 0.01). At six months, blebs with microcysts were 62.5% (group one) and 76.7% (group two). Postoperative complications were observed in 12 eyes (25%) for group one and in 5 eyes (11%) for group two (p = 0.06). No specific complications related to the use of is-ePRGF were identified.Topical is-ePRGF seems to reduce IOP and the rate of complications in the medium term after NPDS, so it can be considered as a possible safe adjuvant to achieve surgical success.
2021-08-31 | Novel combination therapy reduces subconjunctival fibrosis after glaucoma filtration surgery in the rabbit model.
Glaucoma filtration surgery (GFS) is limited by subconjunctival, episcleral and scleral fibrosis sealing the trabeculectomy and scarring the filtering bleb. Mitomycin-C (MMC) is commonly applied intraoperatively to the subconjunctival and/or intrascleral space to reduce scarring and promotes GFS success but is associated with postoperative scleral melting and bleb leaks. IP-10 peptide (IP-10p), an ELR-negative CXC chemokine mimetic and inhibitor of fibroblast function, may be an alternative or adjunct to current postoperative GFS treatments. This study sought to determine if IP-10p produces histological changes in tissue remodelling, vascularity and fibrosis that enhance bleb survival after GFS. Rabbits underwent tube-assisted filtration surgery on the right eye with either: (a) IP-10p injected into bleb at time of surgery and postoperative days 2, 4 and 7, (b) intraoperative MMC or (c) intraoperative MMC plus IP-10p injected into bleb at time of surgery and postoperative days 2, 4 and 7. Left contralateral eyes were treated with balanced salt solution (BSS). IP-10p-treated blebs demonstrated reduced collagen deposition, cellularity and overall reduction of scar formation compared to BSS-control. Bleb vascularity was reduced compared to BSS-control and MMC treatment groups. Additionally, IP-10p/MMC treated eyes demonstrated an increased number of conjunctival goblet cells in bleb histology compared to the dramatic loss seen with MMC treatment alone. This study demonstrates that IP-10p significantly reduces histological scarring compared to BSS or MMC alone, does not damage the conjunctiva to the extent of current standards, and may be an alternative or adjunct to MMC for those undergoing GFS.
2018-08-01 | Matricellular Protein Levels in Aqueous Humor and Surgical Outcomes of Trabeculectomy
Purpose: The purpose of this study was to quantify levels of three matricellular proteins in the aqueous humor in patients with previous acute primary angle closure (APAC) and investigate their correlation with bleb morphology and surgical outcomes of trabeculectomy. Methods: In this prospective study, aqueous humor samples were collected from 40 previous APAC eyes. Concentrations of three matricellular proteins—secreted protein acidic and rich in cysteine (SPARC), thrombospondin-2, and osteopontin—were measured using multiplexed immunoassays kits. Intraocular pressure was measured using Goldmann application tonometry. Bleb morphology was assessed using anterior segment optical coherence tomography, and bleb score was calculated according to bleb size and reflectivity. Results: When previous APAC eyes were divided according to surgical outcome 18 months after trabeculectomy, SPARC protein was significantly higher in aqueous humor in the failure group (P = 0.009). When previous APAC eyes were divided according to SPARC level, eyes with low SPARC levels had significantly higher overall success rate compared with eyes with high SPARC levels (P = 0.005 for complete success and P = 0.018 for qualified success). Multiple logistic regression analyses showed that eyes with higher levels of SPARC were more likely to have a failed filtration surgery than were eyes with lower levels of SPARC. For complete success, P = 0.006 and odds ratio (OR) = 6.458; for qualified success, P = 0.033 and OR = 2.608. The level of SPARC was found to have a positive correlation with bleb score (P < 0.001, R2 = 0.471). Conclusions: In previous APAC patients, the SPARC level in aqueous humor is a prognostic factor for surgical results of trabeculectomy. Modulation of SPARC expression may have potential clinical applications after filtration surgery.
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Drug Discovery Landscape
5 orphan drug designations for Scarring in glaucoma filtration surgical procedures.
5 orphan drug designations for Scarring in glaucoma filtration surgical procedures.
Drug | Therapy type | Regulator | Orphan designation | Approval | Sponsor |
|---|---|---|---|---|---|
Antisense oligonucleotide directed against TGF-beta2 mRNA | oligonucleotides | EMA | 2015-06-19 | — | Isarna Therapeutics GmbH |
synthetic 14-mer phosphorothioate antisense oligonucleotide directed against TGF-beta2 mRNA | oligonucleotides | FDA | 2015-06-04 | — | Isarna Therapeutics GmbH |
4-(4-Methoxy-phenylamino)-6-methylcarbamyl-quinoline-3-carboxylic acid | small molecules | FDA | 2015-03-24 | — | Clanotech AB |
tranilast | small molecules | FDA | 2010-12-23 | — | Esperante Development B.V. |
Zinpentraxin alfa [PRM-151] | proteins | EMA | 2009-10-09 | — | [INACTIVE] Appletree Europe S.à.r.l. |
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