MiR-146a reduces fibrosis after glaucoma filtration surgery in rats.

PURPOSE: To explore the impact of microRNA 146a (miR-146a) and the underlying mechanisms in profibrotic changes following glaucoma filtering surgery (GFS) in rats and stimulation by transforming growth factor (TGF)-ß1 in rat Tenon's capsule fibroblasts. METHODS: Cultured rat Tenon's capsule fibroblasts were treated with TGF-ß1 and analyzed with microarrays for mRNA profiling to validate miR-146a as the target. The Tenon's capsule fibroblasts were then respectively treated with lentivirus-mediated transfection of miR-146a mimic or inhibitor following TGF-ß1 stimulation in vitro, while GFS was performed in rat eyes with respective intraoperative administration of miR-146a, mitomycin C (MMC), or 5-fluorouracil (5-FU) in vivo. Profibrotic genes expression levels (fibronectin, collagen Iα, NF-KB, IL-1ß, TNF-α, SMAD4, and α-smooth muscle actin) were determined through qPCR, Western blotting, immunofluorescence staining and/or histochemical analysis in vitro and in vivo. SMAD4 targeting siRNA was further used to treat the fibroblasts in combination with miR-146a intervention to confirm its role in underlying mechanisms. RESULTS: Upregulation of miR-146a reduced the proliferation rate and profibrotic changes of rat Tenon's capsule fibroblasts induced by TGF-ß1 in vitro, and mitigated subconjunctival fibrosis to extend filtering blebs survival after GFS in vivo, where miR-146a decreased expression levels of NF-KB-SMAD4-related genes, such as fibronectin, collagen Iα, NF-KB, IL-1ß, TNF-α, SMAD4, and α-smooth muscle actin(α-SMA). Additionally, SMAD4 is a key target gene in the process of miR-146a inhibiting fibrosis. CONCLUSIONS: MiR-146a effectively reduced TGF-ß1-induced fibrosis in rat Tenon's capsule fibroblasts in vitro and in vivo, potentially through the NF-KB-SMAD4 signaling pathway. MiR-146a shows promise as a novel therapeutic target for preventing fibrosis and improving the success rate of GFS.

Using a Novel, Subconjunctival, Sustained-Release Mitomycin C Formulation in a Rabbit Model of Filtration Surgery with Gel Stent Implantation.

Purpose: To investigate gel stent implantation with and without intraoperative sustained-release mitomycin C (MMC SR) in a rabbit model for gel stent implantation, and to examine aqueous humor outflow (AHO) postimplantation. Methods: Four groups of rabbits were included. Group 1 was untreated (control). Groups 2, 3, and 4 received the gel stent without MMC, with MMC solution (subconjunctival injection), and with MMC SR (subconjunctival injection), respectively. Intraocular pressure (IOP) and AHO were assessed via tonometry and indocyanine green-based angiography, respectively. The main efficacy measure was change in IOP from baseline. Results: Following gel stent implantation, Groups 2, 3, and 4 maintained ≥20% IOP reduction (response) for a median duration of 1 week, 6.5 weeks, and 30 weeks, respectively. Angiography showed normal aqueous humor drainage (Group 1) beginning at the perilimbal trabecular plexus and continuing posteriorly to episcleral outflow vessels. Following implantation, drainage occurred preferentially and directly into the subconjunctival bleb. Conclusions: Gel stent implantation with MMC SR was most effective in achieving sustained, long-term IOP reduction in the rabbit model, compared with implantation with or without MMC solution. Bleb presence and the postimplantation aqueous angiography results indicated redirection of the AHO to the subconjunctival vasculature and presumed lymphatics, suggesting efficient glaucoma filtration to lower IOP in this model. This rabbit model and aqueous angiography may help refine understanding of the mechanism of action of minimally invasive glaucoma surgeries and ultimately translate to improved surgical devices and procedures for patients with glaucoma.

[Wound healing after trabeculectomy : What and when in postoperative aftercare?] / Wundheilung nach Trabekulektomie : Was wann in der postoperativen Nachsorge?

Excessive wound healing in filtering glaucoma surgery is a key factor for a failed surgery. After the introduction of trabeculectomy in the 1960s many factors associated with an increased fibrotic reaction were recognized and methods were developed to influence postoperative wound healing. These range from the perioperative use of anti-inflammatory drugs and antimetabolites to the use of newer chemical compounds that influence the morphology of postoperative fibroblast growth. In the routine clinical practice, the fine tuning of therapeutic decisions plays a decisive role in the success or failure of filtration surgery.

The Frequency of Intraocular Pressure Elevation, Incidence of Secondary Glaucoma, and Surgical Treatment With Postoperative Complications in Pediatric and Adult Patients With Uveitis.

Purpose To determine the etiology and anatomic localization of uveitis, the frequency of intraocular pressure (IOP) elevation, and the type of secondary glaucoma and to assess the medical, surgical, and postoperative complications in adult and pediatric patients with acute or chronic uveitis. Methods A total of 307 eyes of 186 patients who were followed up in the Uvea-Behçet Unit of the Ophthalmology Department, Erciyes University, Turkey, were included in the study. Demographic, ocular, and systemic data were recorded; ophthalmological examinations were performed; and recurrences and complications of uveitis were identified. The eyes with IOP over 22 mmHg, types of secondary glaucoma, their etiologies, efficiency of medical and surgical treatments, and complications were recorded. Results The mean age was 33 ± 12 years (range: 6-65). Of the 186 patients, diagnoses were as follows: idiopathic uveitis in 84 (45.2%), Behçet disease in 65 (34.9%), ankylosing spondylitis in eight (4.3%), juvenile idiopathic arthritis in five (2.7%), herpetic keratouveitis in three (1.6%), Fuchs iridocyclitis in three (1.6%), Vogt-Koyanagi-Harada syndrome in three (1.6%), tuberculosis uveitis in three (1.6%), Crohn disease in three (1.6%), ocular toxoplasmosis in two (1.1%), multiple sclerosis in two (1.1%), Lyme disease in two (1.1%), rheumatoid arthritis in two (1.1%) and tubulointerstitial nephritis in one patient (0.5%). Secondary glaucoma was detected in 67 (21.9%) of 307 eyes, which developed in 13.7% and 26.8% of the eyes with acute and chronic uveitis, respectively. Of 67 eyes, it was open-angle glaucoma in 58 (86.5%), angle-closure glaucoma in six (9.0%), and neovascular glaucoma in three (4.5%). Control of IOP was achieved by medical therapy in 53 eyes (79.1%) and by surgery in 12 eyes (17.9%), whereas evisceration was required in two eyes (3.0%). Laser iridotomy was performed in four eyes (33.4%), trabeculectomy with mitomycin-C (MMC) in six eyes (50.0%), laser iridotomy plus trabeculectomy with MMC in one eye (8.3%), and express mini shunt implantation in one eye (8.3%). After surgery, IOP was controlled without anti-glaucomatous agents in six eyes (50%) and with anti-glaucomatous agents in the remaining six eyes (50.0%). Conclusion Secondary glaucoma is one of the most important complications of uveitis and may result in severe visual impairment. Early diagnosis and appropriate treatment can prevent these potential complications.

Changes in intraocular pressure following intravitreal dexamethasone implant in patients with history of glaucoma filtration surgery.

PURPOSE: This study aimed to evaluate changes in intraocular pressure following intravitreal dexamethasone implant injection, specifically in patients undergoing glaucoma filtration surgery. METHODS: The degree of increase in intraocular pressure was compared retrospectively among three groups. Group 1 comprised patients who underwent prior glaucoma filtration surgery (54 eyes). Group 2 included patients with or suspected glaucoma without such surgical history (20 eyes). Group 3 included patients without glaucoma (33 eyes). Pressure measurements were taken before the injection and at 1, 2, 3, and 6 months post-injection. A subgroup analysis was performed for pressure > 35 mmHg, > 30 mmHg, > 25 mmHg, and a difference > 10 mmHg between the peak and baseline pressure. RESULTS: Group 1 consistently displayed lower pressures compared with Group 2, with significant difference at both 1- and 6-month post-injections (15.09 mmHg vs. 18.10 mmHg, P = 0.042 and 13.91 mg vs. 17.25 mmHg, P = 0.040). The proportion of patients in Group 1 and Group 3 with pressures > 25 mmHg, > 30 mmHg, and a difference > 10 mmHg did not significantly differ (15.6% vs. 9.5%, P = 0.231; 3.1% vs. 2.3%, P = 0.867; and 17.1% vs. 7.1%, P = 0.231). Notably, Group 2 exhibited a significantly higher proportion within each category (> 25 mmHg, 24.0%; > 30 mmHg, 20.0%; > 10 mmHg difference, 28.0%). CONCLUSION: Intravitreal dexamethasone implant did not increase the risk of elevated intraocular pressure in patients with a history of glaucoma filtration surgery compared with patients with suspected glaucoma; the risk was similar to those without glaucoma.

Bleb vessel density as a predictive factor for surgical revisions after Preserflo Microshunt implantation.

PURPOSE: Bleb failure is a common complication after glaucoma filtration surgery. Different bleb classification schemes incorporating filtration bleb vascularization have been proposed, but the reported correlation with intraocular pressure (IOP) has been variable, possibly because of subjective vascularization grading. The purpose of the present study was to evaluate bleb vascularization after Preserflo Microshunt (PM) implantation using anterior segment OCT-angiography (AS-OCTA) as a biomarker for bleb failure. METHODS: Twenty-three eyes of twenty-three patients underwent PM implantation. Up to 12 months after surgery PM scleral passage-centred AS-OCTA measurements (PLEX Elite 9000) for bleb-vessel density (BVD) determination were performed and IOP as well as necessity for surgical revisions (needling and open revision) were documented. After multi-step image analysis (region of interest definition, artefact removal, binarization, BVD calculation), the predictive value of early postoperative BVD for surgical revisions was assessed using logistic regression modelling. RESULTS: Baseline IOP (23.57 ± 7.75 mmHg) decreased significantly to 8.30 ± 2.12, 9.17 ± 2.33 and 11.70 ± 4.40 mmHg after 1, 2 and 4 week(s), and 13.48 ± 5.83, 11.87 ± 4.49, 12.30 ± 6.65, 11.87 ± 3.11 and 13.05 ± 4.12 mmHg after 2, 3, 6, 9 and 12 month(s), respectively (p < 0.001). Nine patients (39%) needed surgical revisions after a median time of 2 months. Bleb vessel densities at 2 and 4 weeks were significantly associated with future surgical revisions upon logistic regression analysis (2 W/4 W likelihood-ratio test p-value: 0.0244/0.0098; 2 W/4 W area under the receiver operating characteristics curve: 0.796/0.909). CONCLUSION: Filtration bleb vessel density can be determined using AS-OCTA in the early postoperative period and is predictive for bleb failure after PM implantation.

Evaluation of Verteporfin as a Novel Antifibrotic Agent in a Rabbit Model of Glaucoma Filtration Surgery: A Pilot Study.

Purpose: Verteporfin is a benzoporphyrin derivative which is Food and Drug Administration-approved for treatment of choroidal neovascularization in conjunction with photodynamic therapy. It has been shown to prevent fibrosis and scar formation in several organs and represents a promising novel antifibrotic agent for glaucoma surgery. The goal of this study is to determine the effect of verteporfin on wound healing after glaucoma filtration surgery. Design: Preclinical study using a rabbit model of glaucoma filtration surgery. Subjects: Eight New Zealand white rabbits underwent glaucoma filtration surgery in both eyes. Methods: Eyes were randomized into 4 study groups to receive a postoperative subconjunctival injection of 1 mg/mL verteporfin (n = 4), 0.4 mg/mL mitomycin C (MMC; n = 4), 0.4 mg/mL MMC + 1 mg/mL verteporfin (n = 4), or balanced salt solution (BSS) control (n = 4). Bleb survival, vascularity, and morphology were graded using a standard scale over a 30-day period, and intraocular pressure (IOP) was monitored. At 30 days postoperative or surgical failure, histology was performed to evaluate for inflammation, local toxicity, and scarring. Main Outcome Measures: The primary outcome measure was bleb survival. Secondary outcome measures were IOP, bleb morphology, and bleb histology. Results: Compared to BSS control blebs, verteporfin-treated blebs demonstrated a trend toward increased surgical survival (mean 9.8 vs. 7.3 days, log rank P = 0.08). Mitomycin C-treated blebs survived significantly longer than verteporfin-treated blebs (log rank P = 0.009), with all but 1 MMC-treated bleb still surviving at postoperative day 30. There were no significant differences in survival between blebs treated with combination verteporfin + MMC and MMC alone. Mitomycin C-treated blebs were less vascular than verteporfin-treated blebs (mean vascularity score 0.3 ± 0.5 for MMC vs. 1.0 ± 0.0 for verteporfin, P < 0.01). Bleb histology did not reveal any significant toxicity in verteporfin-treated eyes. There were no significant differences in inflammation or scarring across groups. Conclusions: Although verteporfin remained inferior to MMC with regard to surgical survival, there was a trend toward increased survival compared with BSS control and it had an excellent safety profile. Further studies with variations in verteporfin dosage and/or application frequency are needed to assess whether this may be a useful adjunct to glaucoma surgery. Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

A deep learning approach to investigate the filtration bleb functionality after glaucoma surgery: a preliminary study.

PURPOSE: To distinguish functioning from failed filtration blebs (FBs) implementing a deep learning (DL) model on slit-lamp images. METHODS: Retrospective, cross-sectional, multicenter study for development and validation of an artificial intelligence classification algorithm. The dataset consisted of 119 post-trabeculectomy FB images of whom we were aware of the surgical outcome. The ground truth labels were annotated and images splitted into three outcome classes: complete (C) or qualified success (Q), and failure (F). Images were prepared implementing various data cleaning and data transformations techniques. A set of DL models were trained using different ResNet architectures as the backbone. Transfer and ensemble learning were then applied to obtain a final combined model. Accuracy, sensitivity, specificity, area under the ROC curve, and area under the precision-recall curve were calculated to evaluate the final model. Kappa coefficient and P value on the accuracy measure were used to prove the statistical significance level. RESULTS: The DL approach reached good results in unraveling FB functionality. Overall, the model accuracy reached a score of 74%, with a sensitivity of 74% and a specificity of 87%. The area under the ROC curve was 0.8, whereas the area under the precision-recall curve was 0.74. The P value was equal to 0.00307, and the Kappa coefficient was 0.58. CONCLUSIONS: All considered metrics supported that the final DL model was able to discriminate functioning from failed FBs, with good accuracy. This approach could support clinicians in the patients' management after glaucoma surgery in absence of adjunctive clinical data.

Incidence of glaucoma filtration surgery from disease onset of open-angle glaucoma.

AIMS: To investigate the rate and risk factors of undergoing glaucoma filtration surgery (GFS) in patients with newly diagnosed open-angle glaucoma (OAG). METHODS: This is a population-based historic cohort study, consisting of 9420 patients older than 45 years diagnosed with OAG during 1997-2010. Follow-up spanned from 1997 to 2017. We obtained data for trabeculectomy (TRE), deep sclerectomy (DS), and glaucoma drainage implant (GDI) surgeries from national administrative healthcare registers by hospital billing data. We plotted the cumulative incidence of GFS and carried out a multivariate Poisson regression analysis adjusted for age, sex, hospital district, systemic comorbidities, and the number of IOP-lowering drugs. We reported incidence rate ratios (IRR) with 95% confidence intervals (CI) for GFS after the onset of OAG. RESULTS: The cumulative incidence of GFS at 5 years from OAG onset was 3.1% and at 10 years 5.4%. Age over 80 years at baseline was associated with lower GFS incidence (IRR 0.51, CI 0.31-0.84). The number of IOP-lowering drugs in the first 2 years of treatment correlated with the risk of GFS increasing from (IRR 3.23, CI 2.32-4.50) for two drugs, (IRR 7.44, CI 5.28-10.47) for three and to (IRR 14.95, CI 10.38-21.52) for four drugs. CONCLUSION: This study characterized the treatment path of OAG from diagnosis to surgical intervention refining the role of GFS among glaucoma therapies.

Managing the ocular surface after glaucoma filtration surgery: an orphan topic.

BACKGROUND: Ocular surface (OS) disorders before glaucoma filtration surgery (GFS) have been considered to play a crucial role influencing the surgical outcome. Conversely, the impact of surgery itself on the OS is almost completely overlooked, though evidence suggest that ocular surface disease (OSD) may be induced in patients by GFS. This review analyzes the determinants involved in the OSD development after GFS, the clinical features and related consequences, the main diagnostic hallmarks, as well as the therapeutic strategies for its management. METHODS: The PubMed database was utilized for the literature examination. Keywords that were searched included ocular surface disease, glaucoma filtration surgery, filtration bleb, post-surgical management, and quality of life. RESULTS: After GFS, OSD is promoted by peri- and post-operative factors, such as the filtration bleb (FB) development, combined surgical approach with phacoemulsification, the use of antifibrotic agents and the reintroduction of antiglaucoma medications. This particular form of OSD that present similar clinical features to mild to moderate dry eye, can be named as post-glaucoma surgery-OSD (PGS-OSD). PGS-OSD may negatively affect the FB functionality, thus potentially hindering the disease control, and significantly worsen the patient quality of life (QOL). CONCLUSIONS: Clinicians are encouraged to routinely include the OS evaluation after GFS and to consider proper management when the occurrence of PGS-OSD worsen the patient's QOL or exert negative effects to the FB functionality. An outline summarizing the main risk factors and the most appropriate therapeutic options to mitigate the PGS-OSD was proposed to support the routine practice.

Evaluation of New and Preexisting Epiretinal Membranes Following Glaucoma Filtration Surgery.

Secondary epiretinal membranes (ERMs) can develop from various causes, including those associated with glaucoma treatments such as trabeculectomy (TLE) and EX-PRESS (EXP) insertion surgery. This study aimed to investigate the occurrence of new ERMs and changes in preexisting ERMs following TLE or EXP insertion. Between April 2018 and March 2019, 102 and 74 eyes that underwent primary and standalone TLE and EXP insertion, respectively, were evaluated. Of these, 48 eyes were included in the TLE group and 32 eyes were included in the EXP group. Optical coherence tomography (OCT) was used to assess preoperative and postoperative ERMs. In the TLE group, postoperative ERMs were observed in one (case 1) (3%) out of 34 eyes without preexisting ERMs and in one (case 2) (7%) out of 14 eyes with preexisting ERMs, showing an increase in ERM stage. In the EXP group, postoperative ERMs were observed in one (case 3) (5%) out of 22 eyes without preexisting ERMs and in one (case 4) (10%) out of 10 eyes with preexisting ERMs, showing a decrease in the ERM stage. Case 1 was a 58-year-old man with primary open-angle glaucoma (POAG) in the left eye who underwent TLE. Although no preoperative ERMs were observed, postoperative ERM was noted at the three-month follow-up. Case 2 was a 49-year-old man with POAG in the right eye who underwent TLE. Although ERM was observed preoperatively, ERM progressed at six months postoperatively. Case 3 was a 59-year-old woman with POAG in the right eye who underwent EXP insertion. No preoperative ERMs were observed, but an ERM was noted at the 15-month follow-up. Case 4 was a 72-year-old woman with steroid-induced glaucoma in the right eye who underwent EXP insertion surgery. A preoperative ERM was present, and the foveal pit was absent; however, the foveal pit was observed at the 12-month follow-up. Despite the low incidence of ERMs, filtration surgery may be associated with ERM development and the progression or regression of preexisting ERMs.

Effectiveness of conjunctival bleb scarring by knock-down of heat shock protein 47 in rat model.

AIM: 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. METHODS: 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-ß1 (TGF-ß1), phospho-Smad2 (pSmad2), phospho-Smad3 (p-Smad3), and phospho-p38 (p-p38) were also analyzed using Western blot. RESULTS: 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-ß1, p-Smad2/3, and p-p38 were dramatically inhibited after treatment with sh-HSP47 (P<0.01). CONCLUSION: 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.

Ex-PRESS Implantation versus Trabeculectomy for Long-Term Maintenance in Patients with Open-Angle Glaucoma.

Purpose: To compare the efficacy of Ex-PRESS implantation (EXP) with that of trabeculectomy (TLE) with mitomycin C for maintaining low target intraocular pressure (IOP) in patients with open-angle glaucoma. Patients and Methods: Patients were randomly assigned to receive EXP or TLE. Surgical success was defined according to three target mean IOP ranges (5 mmHg ≤ IOP ≤ 18 mmHg [criterion A], 5 mmHg ≤ IOP ≤ 15 mmHg [criterion B], and 5 mmHg ≤ IOP ≤ 12 mmHg [criterion C]) representing reductions of at least 20% below the baseline on two consecutive follow-up visits 3 months post-surgery, with or without antiglaucoma medication and without further glaucoma surgery. Participants were divided into three subgroups based on baseline mean deviation (MD) values: early (MD ≥ -6 dB), moderate (-6 dB > MD ≥ -12 dB), and advanced (-12 dB > MD). Survival rates were calculated by subgroup. Results: A total of 73 patients, including 30 in the EXP group and 43 in the TLE group, were included in the study. No significant differences in baseline ocular or demographic characteristics were found between the two groups. No significant difference in IOP was noted every 6 months. After the 3-year follow-up, success rates were A) 60.0% and 60.2%, B) 45.7% and 58.1%, and C) 31.5% and 40.5% for the EXP and TLE groups, respectively. Moreover, there was no difference in success rate based on glaucoma level. Many glaucoma medications administered before surgery were associated with a higher failure rate in the TLE group but not in the EXP group. Conclusion: Both procedures resulted in similar IOP reductions and success rates for a low target IOP. The number of preoperative glaucoma medications was a risk factor for TLE failure.

The Role of STAT3 Signaling Pathway Activation in Subconjunctival Scar Formation after Glaucoma Filtration Surgery.

Scar formation resulting from overly active wound healing is a critical factor in the success rate of glaucoma filtration surgery (GFS). IL-6 and TGF-ß have been implicated in the pathogenesis of fibrogenesis. In addition, the signal transducer and activator of transcription 3 (STAT3) can be activated by numerous cytokines and growth factors, including IL-6 and TGF-ß1. Thus, STAT3 activation may integrate common profibrotic pathways to promote fibrosis. In this study, an increase in p-STAT3 was observed in activated HTFs. Inhibiting STAT3 in cultured HTFs by pharmacological inactivation reversed the fibrotic responses, such as fibroblast migration, the differentiation of resting fibroblasts into myofibroblasts and the deposition of ECM, mediated by IL-6 and TGF-ß1. Moreover, the expression of suppressor of cytokine signaling 3 (SOCS3) was decreased in HTFs cultured with IL-6 and TGF-ß1, and SOCS3 overexpression rescued ECM deposition, α-SMA expression and migration in IL-6- and TGF-ß1-stimulated HTFs by inactivating STAT3. Finally, S3I-201 treatment inhibited profibrotic gene expression and subconjunctival fibrosis in a rat model of GFS. In conclusion, our data suggests that STAT3 plays a central role in fibrosis induced by different profibrotic pathways and that STAT3 is a potential target for antifibrotic therapies following GFS.

Plasma Rich in Growth Factors as an Adjuvant Agent in Non-Penetrating Deep Sclerectomy.

BACKGROUND: 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). METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

A Degradable Sustained-Release Drug Delivery System for Bleb-Forming Glaucoma Surgery.

Fibrosis of the filtering bleb is one of the main causes of failure after bleb-forming glaucoma surgery. Intraoperative application of mitomycin C (MMC) is the current gold standard to reduce the fibrotic response. However, MMC is cytotoxic and one-time application is often insufficient. A sustained-release drug delivery system (DDS), loaded with MMC, may be less cytotoxic and equally or more effective. Two degradable (polycaprolactone (PCL) and polylactic-co-glycolic acid (PLGA)) MMC-loaded DDSs are developed. Release kinetics are first assessed in vitro followed by rabbit implants in conjunction with the PRESERFLO MicroShunt. As a control, the MicroShunt is implanted with adjunctive use of a MMC solution. Rabbits are euthanized at postoperative day (POD) 28 and 90. The PLGA and PCL DDSs release (on average) 99% and 75% of MMC, respectively. All groups show functioning blebs until POD 90. Rabbits implanted with a DDS show more inflammation with avascular thin-walled blebs when compared to the control. However, collagen is more loosely arranged. The PLGA DDS shows less inflammation, less foreign body response (FBR), and more complete degradation at POD 90 when compared to the PCL DDS. Further optimization with regard to dosage is required to reduce side effects to the conjunctiva.

Anti-scarring effects of conbercept on human Tenon's fibroblasts: comparisons with bevacizumab.

BACKGROUND: Safely inhibiting the formation of scar in the glaucoma filtration surgery (GFS) has always been an issue for clinical glaucoma doctors. Anti-vascular endothelial growth factor (VEGF) agents can reduce angiogenesis, and anti-placental growth factor (PIGF) agents can affect reactive gliosis. However, the effect of conbercept, which can bind to both VEGF and PIGF, on human Tenon's fibroblasts (HTFs) is unknown. METHODS: HTFs were cultured in vitro and treated with conbercept or bevacizumab (BVZ). No drug was added to the control group. The effects of drugs on cell proliferation were assessed using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, and the collagen type I alpha1(Col1A1) mRNA expression level was measured using quantitative polymerase chain reaction (qPCR). HTF cell migration after drug interventions was evaluated using the scratch wound assay along with the measurement of the expression levels of VEGF and PIGF in human umbilical vein endothelial cells (HUVECs) using enzyme-linked immunosorbent assay, as well as the detection of the VEGF(R) mRNA expression level in HTFs using qPCR. RESULTS: After the addition of conbercept (0.01, 0.1, and 1 mg/mL) to the cultured HTFs or HUVECs, no significant cytotoxicity was observed compared with the control group, while the cytotoxicity of 2.5 mg/mL BVZ on HTFs was obvious. Conbercept significantly inhibited HTF cell migration and Col1A1 mRNA expression level in HTFs. It was superior to BVZ in inhibiting HTF migration. After the intervention with conbercept, the expression level of PIGF and VEGF in HUVECs significantly decreased; and the inhibitory effect of conbercept on the expression level of VEGF in HUVECs was weaker than that of BVZ. Conbercept was more advantageous than BVZ in inhibiting the expression level of VEGFR-1 mRNA in HTFs. However, its effect in terms of inhibiting the expression level of VEGFR-2 mRNA in HTFs was weaker than that of BVZ. CONCLUSION: The results suggested the low cytotoxicity and significant anti-scarring effect of conbercept in HTF with significant anti-PIGF and inferior anti-VEGF effects compared with BVZ, thus providing a better understanding of the role of conbercept in the GFS wound healing process.

The Influence of Design Modifications and Microstructured Surface Topographies on Bleb Survival after Glaucoma Tube Shunt Implantation.

Lowering intraocular pressure (IOP) by placement of a glaucoma shunt is an effective treatment for glaucoma. However, fibrosis of the outflow site can hamper surgical outcome. In this study, the antifibrotic effect of adding an endplate (with or without microstructured surface topographies) to a microshunt made of poly(styrene-block-isobutylene-block-styrene) is investigated. New Zealand white rabbits are implanted with a control implant (without endplate) and modified implants. Afterward, bleb morphology and IOP is recorded for 30 days. After killing of the animals, eyes are collected for histology, Addition of an endplate extended bleb survival, Topography-990 has the longest recorded bleb-survival time. Histology reveals that the addition of an endplate increases the presence of myofibroblasts, macrophages, polymorphonuclear cells, and foreign body giant cells compared to the control. However, an increased capsule thickness and inflammatory response are observed in the groups with surface topographies, The addition of an endplate results in prolonged bleb survival, demonstrating that engineering of the shape of glaucoma implants could prolong bleb functionality. Future research should further elaborate the effect of surface topographies on long-term bleb survival, since an increased presence of pro-fibrotic cells and increased capsule thickness are observed compared to the control.

Novel Therapies for the Prevention of Fibrosis in Glaucoma Filtration Surgery.

Conjunctival fibrosis remains the major impediment to the success of glaucoma filtration surgery. Anti-metabolites remain the gold standard for mitigating post-surgical fibrosis, but they are associated with high complication rates and surgical failure rates. Establishing a more targeted approach to attenuate conjunctival fibrosis may revolutionize the surgical approach to glaucoma. A new strategy is needed to prevent progressive tissue remodeling and formation of a fibrotic scar, subsequently increasing surgical success and reducing the prevalence of glaucoma-related vision loss. Advancements in our understanding of molecular signaling and biomechanical cues in the conjunctival tissue architecture are broadening the horizon for new therapies and biomaterials for the mitigation of fibrosis. This review aims to highlight the strategies and current state of promising future approaches for targeting fibrosis in glaucoma filtration surgery.

Trend of glaucoma internal filtration surgeries in a tertiary hospital in China.

AIM: To evaluate the trend of glaucoma internal filtration surgeries for inpatients between 2015 and 2021 at the Eye Hospital of Wenzhou Medical University. METHODS: A review of the medical records of inpatients who had been diagnosed with glaucoma and received anti-glaucoma surgery between January 1, 2015 and December 31, 2021 was conducted. The glaucoma diagnosis in this study included primary open angle glaucoma, primary angle-closure glaucoma, secondary glaucoma, and paediatric glaucoma. The types of surgeries were categorised as internal filtration, external filtration, and cyclodestruction surgery based on the pathway of aqueous humor outflow. The trend of these glaucoma surgeries in the sample of patients with different types of glaucoma was then analysed. RESULTS: The number of patients hospitalised for glaucoma surgery increased yearly, from 752 in 2015 to 1373 in 2021, at the Eye Hospital of Wenzhou Medical University. Regarding the patients diagnosed with primary open angle glaucoma, internal filtration surgery increased from 27.40% of the sample to 54.40% of the sample, while external filtration surgery decreased from 71.50% to 44.20% between 2015 and 2021. For paediatric glaucoma, internal filtration surgery increased from 37.50% in 2015 to 88.20% in 2021. Whilst different types of surgeries were performed on the sample of patients with secondary glaucoma, the proportion of internal filtration surgery also showed an increase from 18.20% in 2015 to 40.90% in 2021. Meanwhile, internal filtration surgery in the patient sample with primary angle-closure glaucoma already accounted for over 70.00% in 2015, and showed a small increase by 2021. CONCLUSION: As surgical technology and surgical experience continue to elevate and improve, the range of glaucoma surgeries are correspondingly evolving. This study find that internal filtration surgeries accounted for an increasing proportion of treatments in the surgical management of glaucoma between 2015 and 2021.