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:
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.
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.
2025-11-10 | 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.
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.
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.
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.
2025-11-10 | 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.
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.
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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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