Short-term Efficacy and Safety of Ologen Collagen Matrix Implantation for Glaucoma Surgery: A Systematic Review and Network Meta-analysis

Short-term Efficacy and Safety of Ologen Collagen Matrix Implantation for Glaucoma Surgery: A Systematic Review and Network Meta-analysis | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Systematic Review Short-term Efficacy and Safety of Ologen Collagen Matrix Implantation for Glaucoma Surgery: A Systematic Review and Network Meta-analysis Xi Zhou This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-5813928/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Importance This network meta-analysis was aimed to evaluate how Ologen will do when combined with different interventions for glaucoma patients. Objective To compare the effectiveness and safety of surgical treatments combined with Ologen and other commonly used treatments for glaucoma. Data Sources and Study Selection This network meta-analysis included randomized or non-randomized controlled trials and retrospective trials that compared interventions concerning Ologen and other treatments for glaucoma. The following databases were searched up to January 1, 2023: PubMed, Embase, Cochrane Library and Web of Science. Data Extraction and Synthesis Data extraction, quality and validity assessing were under the guidelines of 'Preferred Reporting Items for Systematic Reviews and Meta-Analyses'. The demographic character of the included patients and outcomes was extracted independently by 2 investigators. Random-effects model was used to pool the estimate values. Mean outcomes and measures Mean differences for intraocular pressure reduction at 12 months postoperatively and the odds ratios for success rate at the end of follow-up time were the primary and secondary outcome. Measurement of outcomes were reported by 95% credibility intervals, and P < 0.05 was considered statistically significantly. Results This meta-analysis included 35 covering 2477 patients. We discussed 17 interventions, of which 10 had relevant outcomes in intraocular pressure reduction and 17 had relevant outcomes in success rate. When the intraocular pressure reduction was discussed, no pairwise comparison was statistically significant. While for success rate, pairwise comparisons that had statistically significant were detailed in the results and appendix section of this text. The best interventions are as follows: glaucoma drainage device combined with Ologen (success rate, surface under the cumulative ranking = 78.9) and trabeculectomy combined with Ologen (intraocular pressure reduction 12 mouths after surgery, surface under the cumulative ranking = 64). Adverse events were also calculated in details. Conclusion and Relevance Glaucoma drainage device combined with Ologen and trabeculectomy combined with Ologen are the most effective interventions for success rate and intraocular pressure reduction at 12 months postoperatively. However, more clinical studies are still in need to confirm this conclusion and to assess the long-term safety of these interventions. Trial Registration PROSPERO Identifier: CRD42023395804 Ophthalmology Figures Figure 1 Figure 2 Figure 3 Figure 4 Key Point Question What is the best intervention when comparing surgical treatments combined with Ologen and other commonly used surgical treatments for glaucoma? Findings In this network meta-analysis of 2477 patients and 17 treatments, trabeculectomy combined with Ologen and glaucoma drainage device combined with Ologen maybe the best interventions for effectiveness and safety, respectively. Meaning Ologen combination in treatments for glaucoma patients may improve surgical outcomes. This meta-analysis could guide ophthalmologists in clinical decision making. Introduction Glaucoma is a chronic optic neuropathy characterized by progressive loss of retinal ganglion cells and corresponding visual field defects. It is one of the leading causes of irreversible blindness worldwide, affecting more than 70 million people 1 . Glaucoma can be classified into four general categories: primary open-angle and angle-closure, and secondary open and angle-closure glaucoma. The most common type in the United States is primary open-angle glaucoma 2 . The main risk factor for glaucoma is elevated intraocular pressure (IOP), which can damage the optic nerve and impair its function 3 . Elevated IOP is the crucial determinant of disease progression, which remains the only modifiable risk factor. Therefore, all current treatments for glaucoma aim to lower the IOP by various methods, such as medications, lasers, and surgeries 4 . Among the surgical options, trabeculectomy and aqueous shunt devices are commonly used for advanced glaucoma that is refractory to medical or laser therapy. Trabeculectomy, first introduced by Cairns in 1968, has been considered the gold standard for glaucoma surgery, as it can achieve low and stable IOP levels 5 , 6 . However, trabeculectomy has a variable success rate ranging from 11–52%, depending on the definition of success and the follow-up duration. Moreover, trabeculectomy is associated with several complications, such as infection, hypotony, bleb leakage, and cataract 7 , 8 . To improve the outcome and safety of trabeculectomy, antimetabolites such as mitomycin C and 5-fluorouracil have been used as adjunctive agents in the intraoperative and postoperative periods. This modified trabeculectomy has become a new trend in the clinical treatment of glaucoma 6 . Glaucoma drainage implant surgeries have become more popular for the treatment of glaucoma in recent years 9 , 10 , especially for refractory cases that fail to respond to medical or laser therapy or previous trabeculectomy 5 . Glaucoma drainage implant surgeries can lower intraocular pressure by diverting aqueous humor from the anterior chamber to a plate or tube that is implanted in the subconjunctival or sub-Tenon space. Compared with trabeculectomy, glaucoma drainage implant surgeries have some advantages, such as less dependence on the conjunctival wound healing process, less risk of hypotony or bleb-related complications, and more predictable intraocular pressure control. However, glaucoma drainage implant surgeries also have some disadvantages, such as higher cost, longer surgical time, higher risk of tube erosion or infection, and lower success rate in some types of glaucoma 11 , 12 . According to some studies, the rate of choosing GDIs for resurgical treatment of glaucoma was 9%, while the rate of choosing modified trabeculectomy with antimetabolites was 29% 13 . A meta-analysis of clinical studies comparing drainage implant surgeries and other operations found no significant difference between drainage valve implantation and trabeculectomy in reducing IOP, postoperative antiglaucoma medications, and success rate. However, drainage valve surgery had significantly fewer postoperative complications and faster recovery of visual acuity than trabeculectomy 14 , 15 . On the other hand, drainage implant surgeries were more expensive than trabeculectomy, and imposed a greater financial burden on most patients 6 . Therefore, it is important to select the appropriate surgical method according to the patients’ individual characteristics. Ologen collagen matrix is a novel biomaterial for glaucoma surgery. It is a degradable, porous, collagen-glycosaminoglycan scaffold that is placed between the conjunctiva and episcleral space to modulate wound healing and reduce scar formation. By doing so, it lowers the resistance to the aqueous humor outflow and maintains the filtration function 16 – 18 . Ologen collagen matrix affects the cellular and molecular events during wound healing, such as the reorganization of myofibroblasts, fibroblasts, and extracellular matrix. The collagen density and structure in Ologen-treated wounds resemble those of normal conjunctival connective tissue 16 , 18 , 19 . Ologen can be used as an adjunctive material in various glaucoma surgical procedures. For example, Ologen matrix with drainage valve implantation, Ologen-augmented trabeculectomy. As phacoemulsification is often combined with drainage valve implantation, which results in significant IOP reduction in the combined procedure 20 . Moreover, lens extraction itself also affects postoperative IOP measurement 21 – 23 . Therefore, whether combined with phacoemulsification or not is also worth discussing as an independent variable. The purpose of this network meta-analysis was to compare the efficacy and safety of commonly used interventions with or without ologen in patients with glaucoma. Methods Data sources We searched Pubmed, Embase, Web of science and Cochrane for studies on the effect of glaucoma surgery with or without ologen, such as ologen-augmented trabeculectomy, drainage valve implantation with ologen insertion, etc. from their inception through January 1, 2023. We did not apply any restrictions on publication year, language or study design. We used medical subject headings and keywords, including ‘glaucoma’, ‘collagen-glycosaminoglycan copolymer’ and ‘ologen’, etc. The details of the search strategy are shown in appendix 1 to 4. Two investigators independently screened the titles and abstracts of the retrieved studies. We contacted the corresponding authors if missing critical data were found. We applied the inclusion and exclusion criteria to the full texts of the selected studies. A third investigator carefully checked the final included studies. Study selection We included studies that met the following criteria: (1) study type: randomised controlled trials (RCTs) or cohort studies; (2) population: patients with glaucoma, whether primary or secondary, open-angle or closed-angle; (3) intervention: comparison of the postoperative effect of different glaucoma surgeries combined with ologen with a control group. (4) outcome variables: availability of at least one of the outcome measures; (5) connection: inclusion of some appropriate studies to maintain the connection of the network during comparison. We excluded studies that had one of the following conditions: (1) follow-up time of < 6 months; (2) small sample size with n < 5; (3) the same surgical method or its modified version in both groups without considering the addition of ologen, for example, a study of drainage valve implantation versus drainage implant surgeries with mitomycin was excluded; (4) drug dose related studies; (5) studies without the required data and the data could not be obtained by contacting the corresponding author, or the corresponding author was unreachable. Outcomes The primary outcome was the mean difference of IOPR (intraocular pressure reduction) after surgery, regardless of whether antiglaucoma medication was used or not. The required data were calculated by the following formula if the mean difference and standard deviation (SD) of IOPR were not provided by the authors 24 , 25 : IOPR = IOP baseline – IOP endpoint , SD IOPR = SD baseline 2 + SD endpoint 2 – (2 × SD baseline × SD endpoint ) 1/2 . We extracted the IOP data at 12 months after surgery from the included studies to reduce bias. If the IOP data at 12 months postoperative were not reported, then the study was excluded from the analysis of IOPR outcome. The secondary outcome was success rate. If there was no common time point reporting the success rate among included studies, we used the success rate of the final follow-up. Data Extraction Two investigators independently extracted the following data from the included studies: (1) demographic data, such as authors’ name, study design, publication year, patients’ age and gender, sample size of discussion group, primary cause of glaucoma and follow-up time; (2) outcome data, such as IOPR at 12 months postoperatively and success rate at the end of follow-up. Quality assessment We used the Cochrane risk of bias tool and the Newcastle-Ottawa scale to assess the quality of randomized/non-randomized controlled trials and retrospective cohort studies, respectively. Two investigators independently performed the quality assessment, and resolved any disagreement by consensus with all investigators. Data Synthesis This network meta-analysis was executed through Stata (Version 17.0). Treatments that compared the surgical effect of ologen and other methods were comprised in this meta-analysis. This meta-analysis was using two indicators, the IOPR at 12 mouth after surgery and success rate to assess the effect of different treating methods. Mean difference and 95% credible interval (CI) were used to analyze the continuous variable, while dichotomous variables using odds ratio (OR). We prepared the network analysis data using the ‘network setup’ command. We drew the network forest and network map using the ‘network forest’ and ‘network map’ commands. We checked the local inconsistency by node splitting and loop-specific approaches. We assessed the heterogeneity of included studies using I 2 and χ 2 statistics and considered it significant if I 2 was > 50% or the P value < 0.05 26,27 . We used the 'Mvmeta’ package to perform the plots of different comparisons, the rankplots based on probabilities and the surface under the cumulative ranking (SUCRA) for different endpoints. We used the Grades of Recommendations Assessment, Development and Evaluation to assess the quality of the outcomes 28 . Strength of Evidence The strength of evidence was assessed by using Grade of Recommendations Assessment, Development and Evaluation (GRADE). Ratings were based on heterogeneity (low, some and major), within-study bias (low, some and major), incoherence (low, some and major), indirectness (low, some and major), imprecision (low, some and major), and reporting bias (suspected or undetected). The strength of evidence was assigned an overall grade of high, moderate, low, or very low by evaluating and weighing the combined results of the above domains 29 . Grades were initially assessed by 1 investigator and then reviewed by all investigators for consensus. Results Identification of the relevant studies We initially searched for 452 articles discussing the effect of Ologen. We excluded 141 articles for duplications, 177 articles by title, and 18 articles by abstracts. We checked the full texts of the remaining articles for eligibility. We excluded 11 articles for being case reports, 16 articles for having inappropriate controls, 18 articles for being non-human research, and 16 articles for being reviews, meta-analyses, letters or conferences. We excluded 23 articles for having unavailable or improper data. We included 32 articles in the final screening (Appendix 5 shows the reference list of screened studies). We added three studies to connect the network of this meta-analysis. We included 35 studies in the final analysis. Figure 1 shows the selection procedure and the details of the added studies. Characteristics of the included studies This network meta-analysis included 2477 patients. The sample size for each group ranged from 8 to 107. The included studies consisted of 18 randomized controlled trials, 4 non-randomized prospective trials and 13 retrospective cohort studies. There were 31 two-arm studies and 4 three-arm studies in total. For the outcome of IOPR at 12 months postoperatively, we included 10 surgical treatments in 19 studies. The surgical treatments were: trabeculectomy (TE) with ologen (TE(Ologen)), TE with antimetabolites (TE(AM)), drainage valve implantation (GDD), GDD with antimetabolites (GDD(AM)), GDD with ologen (GDD(Ologen)), GDD(AM) and ologen (GDD(AM + Ologen)), TE(AM) and ologen (TE(AM + Ologen)), TE(AM) and anti-vascular endothelial growth factor (antiVEGF) soaked ologen (TE(AM + antiVEGF soaked Ologen)), TE with viscotrabeculotomy-synechiolysis (TE(VTS)) and TE with perfluoropropane (TE(C3F8)). For the outcome of success rate, we included 17 surgical interventions in 31 studies. The surgical interventions were: TE, TE(Ologen), TE(AM), GDD, GDD(AM), GDD(Ologen), GDD(AM + Ologen), TE(AM + Ologen), TE(AM + antiVEGF soaked Ologen), TE(VTS), TE(C3F8), phacoemulsification with TE and AM (phacoTE(AM)), phacoTE with Ologen (phacoTE(Ologen)), phacoemulsification with GDD and AM (phacoGDD(AM)), phacoGDD with Ologen and antimetabolites (phacoGDD(AM + Ologen)), TE(AM) and GDD (TE(AM + GDD)) and TE(Ologen) and GDD (TE(Ologen + GDD)). Table 1 shows the definitions of the acronyms. For the outcome of IOPR at 12 months after surgery, we included 19 studies. The comparisons were: TE(Ologen) vs TE(AM) (10 studies), TE(AM) vs GDD(AM) (1 study), TE(AM + Ologen) vs TE(AM) + anti-VEGF soaked Ologen (1 study), TE(Ologen) vs TE(C3F8) (1 study), TE(AM) vs TE(AM + Ologen) (3 studies), GDD(Ologen) vs GDD(AM + Ologen) (1 study), GDD(AM + Ologen) vs GDD(AM) (1 study), TE(Ologen) vs TE(VTS) (1 study), TE(AM) vs TE(AM + antiVEGF soaked Ologen) (1 study), GDD vs GDD(Ologen) (2 studies), and GDD(Ologen) vs GDD(AM) (1 study). For the outcome of success rate, we included 31 studies. The comparisons were: TE(Ologen) vs TE(AM) (8 studies), TE(Ologen) vs TE(VTS) (1 study), TE(AM) vs phacoTE(AM) (1 study), phacoGDD(AM) vs GDD(AM + Ologen) (1 study), phacoGDD(AM + Ologen) vs GDD(AM) (1 study), TE(Ologen) vs TE(C3F8) (1 study), TE(AM) vs GDD(AM) (1 study), GDD(AM + Ologen) vs phacoGDD(AM + Ologen) (1 study), GDD(AM + Ologen) vs GDD(AM) (3 studies), TE(AM + GVI) vs TE(Ologen + GDD) (1 study), TE(Ologen) vs TE (1 study), TE(AM) vs TE(AM + Ologen) (3 studies), TE(AM) vs TE(AM + antiVEGF soaked Ologen) (1 study), TE(AM + GVI) vs TE(AM + Ologen) (1 study), GDD(AM) vs phaco GDD(AM) (1 study), GDD(Ologen) vs GDD (5 studies), TE(AM + Ologen) vs TE(AM + antiVEGF soaked Ologen) (1 study), phacoTE(AM) vs phacoTE(Ologen) (4 studies), phacoGVI (AM) vs phacoGDD(Ologen + AM) (1 study), and TE(AM) vs GDD (1 study). The number of patients in different surgical treatment groups varied by the outcome of IOPR at 12 months after surgery. The groups were: TE(Ologen) (278 patients), TE(AM) (410 patients), GDD(Ologen) (38 patients), GDD (29 patients), TE(AM + Ologen) (90 patients), TE(AM + antiVEGF soaked Ologen) (44 patients), GDD(AM + Ologen) (6 patients), GDD(AM) (101 patients), TE(VTS) (22 patients) and TE(C3F8) (28 patients). The total number of patients included for the outcome of success rate in different surgical treatments were: TE(Ologen) (256 patients), TE(AM) (596 patients), GDD(Ologen) (89 patients), GDD (278 patients), TE(AM + Ologen) (154 patients), TE(AM + antiVEGF soaked Ologen) (46 patients), TE (20 patients), phacoTE(AM) (200 patients), phacoTE(Ologen) (118 patients), GDD(AM + Ologen) (90 patients), phacoGDD(AM) (12 patients), phacoGDD(AM + Ologen) (19 patients), GDD(AM) (176 patients), TE(VTS) (24 patients), TE(C3F8) (28 patients), TE(AM + GVI) (70 patients), and TE(Ologen + GDD) (49 patients). The success criteria for the 35 studies were defined by the authors and are summarized in Appendix 6. The demographic characteristics of each study are shown in Table 2. Quality assessment Of the 18 randomized clinical trials (RCTs), 6 used computer-generated random numbers and 5 did not report the randomization method. The other 7 RCTs used various methods, such as drawing lots, coin flipping, sealed envelopes, consort guidelines, permuted block randomization, randomized blocks design, and single-and-even number randomization. Only 3 RCTs reported the blinding method and 2 reported non-blinding. The rest did not mention blinding in the full text. Fourteen RCTs provided complete outcome data and 4 provided incomplete data. The risk of bias summary for all RCTs is shown in appendix 7. The quality of the 13 included retrospective cohort studies was assessed using the Newcastle-Ottawa Quality Assessment Scale. Three studies scored 8 points, 7 scored 7 points, and 3 scored 6 points (Appendix 8). The quality of the 4 non-randomized studies was evaluated using the Methodological Index for Non-randomized Studies, and all scored higher than 16 points 30 . Details are shown in Appendix 9. The results of meta-analysis The network plots for success rate and IOPR at 12 months postoperative are shown in Fig. 2. The forest plots are shown in Fig. 3. The results of pairwise meta-analysis of IOPR at 12 months and success rate are presented in appendix 10. Nineteen studies involving 1046 eyes are included in the discussion of IOPR at 12 mouth postoperatively (Fig. 2). However, no statistically significant difference was found when comparing TE(Ologen) and other interventions. The success rate was assessed for 2191 eyes from 31 studies involving 17 interventions. The network forest plots are shown in Fig. 3. Compared with TE(Ologen), PhacoGDD(AM) (OR, -0.75; 95% CI, -2.20 to 0.70), TE(C3F8) (OR, -0.64; 95% CI, -2.08 to 0.79), TE(AM + GDD) (OR, -0.95; 95% CI, -2.65 to 0.76), and TE(Ologen + GDD) (OR, 0.07; 95% CI, -0.81 to 0.96) showed significant differences. Compared with TE(AM + antiVEGF soaked Ologen), TE (OR, -0.49; 95% CI, -1.88 to 0.90), PhacoTE(Ologen) (OR, -0.34; 95% CI, -1.25 to 0.57), PhacoGDD(AM) (OR, -1.92; 95% CI, -4.67 to 0.83), TE(C3F8) (OR, -1.81; 95% CI, -4.55 to 0.93), and TE(AM + GDD) (OR, -2.12; 95% CI, -5.02 to 0.78) showed significant differences. Compared with GDD(AM), TE(VTS) (OR, -0.26; 95% CI, -1.46 to 0.94), TE(C3F8) (OR, -1.13; 95% CI, -2.78 to 0.52), TE(AM + GDD) (OR, -1.43; 95% CI, -3.33 to 0.46), and TE(Ologen + GDD) (OR, -0.41; 95% CI, -1.61 to 0.79) showed significant differences. Compared with TE(VTS), TE(C3F8) (OR, -0.87; 95% CI, -2.25 to 0.51), TE(AM + GDD) (OR, -1.17; 95% CI, -2.84 to 0.49), and TE(Ologen + GDD) (OR, -0.16; 95% CI, -0.94 to 0.63) showed significant differences. A significant difference was also found between TE(C3F8) and TE(AM + GDD) (OR, -0.31; 95% CI, -1.24 to 0.63) and between GDD(AM + Ologen) and PhacoGDD(AM) (OR, -0.26; 95% CI, -1.40 to 0.87). No significant difference was found between any other two interventions. Details are shown in Appendix 10. The probability ranking plot and the SUCRA are shown in Appendix 11. Table 3 shows the specific ranking for each intervention for success rate and IOPR. For IOPR at 12 months postoperatively, TE(Ologen) had the highest probability of being the best among the 10 interventions, followed by TE, TE(C3F8), and TE(VTS). GDD(Ologen) was the best intervention for success rate, while PhacoTE(AM), GDD, and PhacoTE(Ologen) ranked lower, respectively. Consistency analysis The inconsistency was assessed by node-splitting analysis, which compared direct and indirect effects (Appendix 12). No significant inconsistency was found, indicating that the results were reliable. The loop-specific analysis showed that the comparisons of closed circles for success rate had no significant inconsistency, but the loop-specific analysis for IOPR showed inconsistency between direct and indirect comparisons (Table 4). Grade of Recommendations Assessment, Development and Evaluation (GRADE) for the outcome measurements The specific details of the GRADE evaluation for success rate and IOPR are shown in Appendix 13 and Appendix 14, respectively. The evaluation of direct comparison in network meta-analysis was similar to that of meta-analysis, and the indirect comparison used the lowest score among the included direct comparisons as its evaluation level. As a result, the evidence included in this network meta-analysis was of moderate, low, or very low quality. Complications Postoperative complications were reported in 31 of the 35 included studies. Twenty-one studies reported 94 cases of postoperative low intraocular pressure, with the following distribution: TE(Ologen), 15 cases; TE(AM), 31 cases; GDD(Ologen), 6 cases; GDD, 4 cases; TE(AM + Ologen), 5 cases; TE(AM + anti-VEGF soaked Ologen), 2 cases; TE, 1 case; PhacoTE(AM), 7 cases; PhacoTE(Ologen), 3 cases; GDD(AM + Ologen), 8 cases; GDD(AM), 11 cases; and TE(C3F8), 1 case. Bleb leak was reported in 30 studies, with 43 cases in total. The distribution of cases was as follows: GDD and TE(AM + Ologen), 1 case each; GDD(Ologen), TE(AM + anti-VEGF soaked Ologen), and PhacoTE(Ologen), 3 cases each; TE(Ologen), 2 cases; TE(AM), 13 cases; TE(GDD + AM), 9 cases; and TE(GDD + Ologen), 8 cases. Bleb failure was reported in 11 studies, with 69 cases in total. The distribution of cases was as follows: GDD(Ologen), GDD, and PhacoTE(Ologen), 6 cases each; GDD(AM + Ologen) and TE(GDD + AM), 1 case each; TE(AM + Ologen) and PhacoTE(AM), 2 cases each; TE(Ologen), 11 cases; TE(AM), 8 cases; TE, 5 cases; GDD(AM), 18 cases; and TE(C3F8), 3 cases. Tube-associated complications, such as tube obstruction, tube exposure, and tube migration, were reported in 3 studies. There were 5 cases each in the GDD(Ologen) and GDD groups. Postoperative intraocular hypertension was reported in 3 studies, with the following distribution of cases: TE(AM), 14 cases; GDD(Ologen), 7 cases; GDD, 14 cases; and GDD(AM), 13 cases. One case of phthisis bulbi in the GDD group was reported in 1 study. Significant loss of vision after surgery was reported in 4 studies. The distribution of cases was as follows: TE(Ologen), GDD, and PhacoTE(AM), 4 cases each; TE(AM), 5 cases; and GDD(Ologen), 3 cases. Corneal edema was reported in 3 studies, with 6 cases in total. The distribution of cases was as follows: GDD(Ologen), 2 cases; GDD, 3 cases; and GDD(AM + Ologen), 1 case. Shallow anterior chamber was reported in 16 studies, with 59 cases in total. The distribution of cases was as follows: TE, PhacoTE(AM), PhacoTE(Ologen), TE(VTS), and TE(C3F8), 1 case each; GDD(Ologen), GDD, and TE(GDD + AM), 4 cases each; TE(Ologen), 18 cases; TE(AM + Ologen), 8 cases; and TE(AM), 18 cases. Anterior chamber exudation was reported in 4 studies, with 31 cases in total. The distribution of cases was as follows: TE(Ologen) and TE(AM), 12 cases each; PhacoTE(AM), 2 cases; and PhacoTE(Ologen), 5 cases. Hyphema was reported in 30 studies, with 45 cases in total. The distribution of cases was as follows: TE(AM + Ologen), TE(AM + anti-VEGF soaked Ologen), and TE, 3 cases each; TE(AM), 10 cases; GDD(Ologen), 6 cases; GDD, 4 cases; TE(VTS), 2 cases; and TE(GDD + AM), 1 case. Vitreous hemorrhage was reported in 2 studies, with 3 cases in total. There was 1 case each in the TE(AM + anti-VEGF soaked Ologen), TE(AM + Ologen), and GDD groups. Choroidal detachment was reported in 15 studies, with 51 cases in total. The distribution of cases was as follows: GDD, PhacoTE(AM), and PhacoTE(Ologen), 4 cases each; TE(GDD + AM) and TE(GDD + Ologen), 2 cases each; TE(Ologen) and TE(AM + Ologen), 8 cases each; TE(AM), 14 cases; and GDD(Ologen), 5 cases. Retinal detachment was reported in 1 study, with 1 case in the GDD group. Two studies reported a total of eight cases of glaucoma recurrence, with 1, 2, 3, and 2 cases in the GDD(Ologen), PhacoGDD(AM + Ologen), GDD(AM + Ologen), and GDD(AM) groups, respectively. In addition to the commonly seen postoperative complications described above, a total of 23 studies reported 201 other cases. These included six cases each in the TE(AM + anti-VEGF soaked Ologen), GDD(AM + Ologen), and GDD(AM) groups; five cases each in the PhacoTE(Ologen) and TE(GDD + AM) groups; 25 cases in the TE(Ologen) group; 69 cases in the TE(AM) group; 12 cases in the GDD(Ologen) group; 20 cases in the GDD group; 33 cases in the TE(AM + Ologen) group; three cases in the PhacoTE(AM) group; nine cases in the TE(VTS) group; and two cases in the TE(C3F8) group. Further details are presented in Appendix 15. Discussion This is the first meta-analysis to evaluate the safety and efficacy of Ologen compared to other commonly used treatments in glaucoma patients. The aim of this study was to explore more effective treatment options. Until now, there have been relatively few meta-analyses concerning Ologen and other interventions, and no network meta-analyses. The most recent meta-analysis, conducted in 2019 by Song et al., compared the efficacy of Ologen and mitomycin in trabeculectomy. The study concluded that trabeculectomy with mitomycin was associated with higher IOP-lowering efficacy, but also a higher incidence of post-surgery complications compared to trabeculectomy with Ologen 31 . Although there have been several clinical studies comparing the efficacy of Ologen with other treatments, a network meta-analysis comparing Ologen and other commonly used treatments in glaucoma patients is still lacking. It is necessary to conduct such a network meta-analysis to compare the use of Ologen collagen matrix with other interventions in glaucoma patients. The results of our analysis suggest that GDD(Ologen) was the most effective intervention in terms of surgical success rate, followed by PhacoTE(AM), with TE ranked last. In terms of IOP reduction at 12 months postoperatively, TE(Ologen) was the most effective intervention, followed by TE(AM). GDD(Ologen), GDD and GDD(AM) were ranked in the bottom three. There are three possible reasons for the discrepancy between the best and worst rankings for IOPR and surgical success rate. First, the inconsistency in follow-up times for the two surgical outcomes among the studies may have contributed to the discrepancy. To avoid bias, only IOP measurements at 12 months postoperatively were included. However, the time point for reporting surgical success rate varied among studies. Although there is insufficient information to conclude whether there are differences between glaucoma drainage device implantation and trabeculectomy for glaucoma treatment, aqueous shunt implantation is considered to be a lower-risk option with a lower risk of failure and is a more favorable choice among surgeons 28 , 32 . As follow-up time increases, fibrosis of the conjunctiva and scarring in trabeculectomy can affect the surgical success rate 33 – 35 . Secondly, differences in the data from studies and interventions included in the discussions of IOP reduction and surgical success rate may also contribute to the discrepancy. For IOP reduction, 19 studies and 10 interventions were included, while for surgical success rate, 31 studies and 17 interventions were included. This study did not categorize different glaucoma drainage devices because there is currently no evidence to support the superiority of one device over another 32 , 36 , 37 . Lastly, asymmetry in the funnel plots for surgical success rate and IOPR suggests the presence of potential bias (Fig. 4). The loop-specific analysis of IOPR showed probable inconsistency between direct and indirect comparisons (Table 4). Therefore, the result that GDD(Ologen) ranked at the bottom of the IOPR list should be interpreted with caution. In summary, the adverse events reported in this meta-analysis are shown in Table 5. First, low IOP, bleb leak, significant loss of vision during follow-up, and choroidal detachment were more commonly seen in the TE(AM) group. Second, tube-associated complications such as tube obstruction, tube exposure, and tube migration were more frequently reported in the GDD(Ologen) and GDD groups. Third, shallow anterior chamber, anterior chamber exudation, and hyphema were more frequently reported in the TE(Ologen) group. Fourth, vitreous hemorrhage was only reported in the GDD, TE(AM + Ologen) and TE(AM + antiVEGF soaked Ologen) group among the 17 interventions. Fifth, low IOP was the most common complication in the TE(Ologen) and TE(AM) groups. Sixth, postoperative intraocular hypertension was the most common complication in the GDD(Ologen) and GDD groups. Seventh, no complications were reported in the PhacoGDD(AM) group. Although the number of complications is relatively small, their incidence varied greatly among groups. Additionally, the complications reported by each study varied, so the results should be interpreted with caution. Finally, the number of patients with complications was concentrated in the TE(Ologen), TE(AM), GDD(Ologen), GDD and TE(AM + Ologen) groups. This may be due to most of the included studies performing pairwise analysis between these interventions. This study has several advantages. First, it is the first network meta-analysis to compare different interventions with or without Ologen. The direct and indirect effects of 17 treatments were compared, and a SUCRA plot was generated to evaluate the rankings of the included interventions. Additionally, the heterogeneity among the evidence was relatively low, making the results more reliable and useful for ophthalmologists when deciding on the most appropriate surgical treatment for glaucoma patients. However, there are also several limitations to this study. First, the GRADE rating for outcome measurements was relatively low, with no high-scored measurements and several very low ratings. Second, the loop-specific analysis of IOP reduction showed inconsistency between direct and indirect comparisons. Third, the interventions discussed for IOPR and surgical success rate were not consistent, with 10 and 17 interventions included, respectively. This inconsistency in the number of interventions may introduce potential bias between the analysis results for the two surgical outcomes. Fourth, the criteria for defining surgical success varied among studies, which could be another source of research bias. Fifth, the number of studies analyzing different intervention groups varied considerably. For example, 13 studies discussed the TE(Ologen) group, while only one study referred to the TE(AM + anti-VEGF soaked Ologen) group. Sixth, the number of outcomes discussed in this network meta-analysis was limited. Only IOPR at 12 months and surgical success rate were included due to the limited categories of postoperative follow-up examinations and data reported in the included studies. If more types of surgical outcomes were included, the reliability of this network meta-analysis would be higher. For instance, differences in best-corrected visual acuity, perimetry results, and glaucoma medication use pre- and postoperatively could also be considered when analyzing different interventions. Seventh, the composition of primary diseases in the included studies was inconsistent. These differences may influence the efficacy of surgery and introduce potential bias. Finally, the number of RCTs was relatively low. This meta-analysis included three types of studies due to the limited number of eligible studies: 18 RCTs, 17 retrospective studies, and 3 non-randomized prospective studies. Some interventions were not included due to a limited number of studies. These limitations may affect the final outcomes and could be improved in future research with more refined study design. Conclusion In conclusion, this network meta-analysis found that GDD(OLogen) and TE(Ologen) were the most effective interventions in terms of surgical success rate and IOPR at 12 months postoperatively, respectively. However, considering the limitations of this network meta-analysis, more well-designed and high-quality trials are needed to include additional interventions beyond those currently discussed. More randomized controlled trials are also needed to strengthen the current conclusions. References Cook C, Foster P (2012) Epidemiology of glaucoma: what's new? Can J Ophthalmol Jun 47(3):223–226. 10.1016/j.jcjo.2012.02.003 Jonas JB, Aung T, Bourne RR, Bron AM, Ritch R, Panda-Jonas S, Glaucoma (2017) Lancet Nov 11(10108):2183–2193. 10.1016/s0140-6736(17)31469-1 Dietze J, Blair K, Havens SJ, Glaucoma (2023) StatPearls . 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J Cataract Refract Surg Nov 35(11):1946–1955. 10.1016/j.jcrs.2009.05.061 Armstrong JJ, Wasiuta T, Kiatos E, Malvankar-Mehta M, Hutnik CML (2017) The Effects of Phacoemulsification on Intraocular Pressure and Topical Medication Use in Patients With Glaucoma: A Systematic Review and Meta-analysis of 3-Year Data. J Glaucoma Jun 26(6):511–522. 10.1097/ijg.0000000000000643 Shingleton BJ, Pasternack JJ, Hung JW, O'Donoghue MW (2006) Three and five year changes in intraocular pressures after clear corneal phacoemulsification in open angle glaucoma patients, glaucoma suspects, and normal patients. J Glaucoma Dec 15(6):494–498. 10.1097/01.ijg.0000212294.31411.92 Hong M, Peng Y, Lai Y, Zheng Q, Hong C (2023) Comparison of Aurolab Aqueous Drainage Implant with Ahmed Glaucoma Valve for refractory glaucoma: a meta-analysis. 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BMJ Open May 24(5):e051794. 10.1136/bmjopen-2021-051794 Berkman ND, Lohr KN, Ansari MT et al (2015) Grading the strength of a body of evidence when assessing health care interventions: an EPC update. J Clin Epidemiol Nov 68(11):1312–1324. 10.1016/j.jclinepi.2014.11.023 Slim K, Nini E, Forestier D, Kwiatkowski F, Panis Y, Chipponi J (2003) Methodological index for non-randomized studies (minors): development and validation of a new instrument. ANZ J Surg Sep 73(9):712–716. 10.1046/j.1445-2197.2003.02748.x Song DS, Qian J, Chen ZJ (2019) Ologen implant versus mitomycin-C for trabeculectomy: A meta-analysis. Med (Baltimore) Jun 98(25):e16094. 10.1097/md.0000000000016094 Tseng VL, Coleman AL, Chang MY, Caprioli J (2017) Aqueous shunts for glaucoma. Cochrane Database Syst Rev Jul 28(7):Cd004918. 10.1002/14651858.CD004918.pub3 Marcos Parra MT, Salinas López JA, López Grau NS, Ceausescu AM, Pérez Santonja JJ (2019) XEN implant device versus trabeculectomy, either alone or in combination with phacoemulsification, in open-angle glaucoma patients. Graefes Arch Clin Exp Ophthalmol Aug 257(8):1741–1750. 10.1007/s00417-019-04341-y Chen G, Li W, Jiang F, Mao S, Tong Y (2014) Ex-PRESS implantation versus trabeculectomy in open-angle glaucoma: a meta-analysis of randomized controlled clinical trials. PLoS ONE 9(1):e86045. 10.1371/journal.pone.0086045 Gedde SJ, Singh K, Schiffman JC, Feuer WJ (2012) The Tube Versus Trabeculectomy Study: interpretation of results and application to clinical practice. Curr Opin Ophthalmol Mar 23(2):118–126. 10.1097/ICU.0b013e32834ff2d1 Suda M, Nakanishi H, Akagi T et al (2018) Baerveldt or Ahmed glaucoma valve implantation with pars plana tube insertion in Japanese eyes with neovascular glaucoma: 1-year outcomes. Clin Ophthalmol 12:2439–2449. 10.2147/opth.S183689 Yalvac IS, Eksioglu U, Satana B, Duman S (2007) Long-term results of Ahmed glaucoma valve and Molteno implant in neovascular glaucoma. Eye 2007/01/01 21(1):65–70. 10.1038/sj.eye.6702125 Tables Table 1 The acronyms of the included interventions Acronym Interventions TE Trabeculectomy TE(AM) TE with antimetabolites GDD Glaucoma drainage device GDD(Ologen) GDD with ologen TE(AM+Ologen) TE(AM) combined with Ologen TE(AM+antiVEGF soaked Ologen) TE(AM) combined with anti-vascular endothelial growth factor (antiVEGF) socked TE(Ologen) TE combined with ologen PhacoTE(AM) phacoemulsification combined with TE(AM) PhacoTE(Ologen) phacoemulsification combined with TE(Ologen) GDD(AM) GDD with antimetabolites PhacoGDD(AM) Phacoemulsification combined with GDD(AM) GDD(AM+Ologen) GDD(AM) combined with Ologen PhacoGDD(AM+Ologen) phacoemulsification combined with GDD(AM+Ologen) TE(VTS) TE with viscotrabeculo tomysynechiolysis TE(C3F8) TE with perfluoropropane TE(GDD+AM) TE(AM) combined with GDD TE(GDD+Ologen) TE(Ologen) combined with GDD Table 2 is available in the Supplementary Files section. Table 3 The results of surface under the cumulative ranking curve (SUCRA) Treatment SUCRA PrBest MeanRank IOPR (12 mouth) TE(Ologen) 64 5.4 4.2 TE(AM) 62.2 4.1 4.4 TE(C3F8) 59 12.6 4.7 TE(VTS) 54.9 9.5 5.1 GDD(AM+Ologen) 53.2 30 5.2 TE(AM+Ologen) 50.5 7.5 5.5 TE(AM+antiVEGF soaked Ologen) 50.3 14.1 5.5 GDD(Ologen) 36.1 7 6.7 GDD 36.5 9.8 6.7 GDD(AM) 33.2 0 7 Success rate GDD(Ologen) 78.9 21.9 4.4 PhacoTE(AM) 74.6 8.6 5.1 GDD 70.2 3.1 5.8 PhacoTE(Ologen) 62.2 8 7.1 PhacoGDD(AM+Ologen) 60.3 9.8 7.4 TE(Ologen+GDD) 60.2 22.7 7.4 TE(VTS) 57.5 10 7.8 GDD(AM+Ologen) 55.9 2.7 8.1 TE(Ologen) 46.1 0.2 9.6 TE(AM) 42.4 0 10.2 GDD(AM) 40.8 0.1 10.5 TE(AM+GDD) 39.2 1.5 10.7 PhacoGDD(AM) 37 2.1 11.1 TE(AM+Ologen) 36 0 11.2 TE(C3F8) 35 3.6 11.4 TE(AM+antiVEGF soaked Ologen) 28 0.2 12.5 TE 25.7 5.6 12.9 *Note: IOPR, intraocular pressure reduction; SUCRA, surface under the cumulative ranking curve. (TE, trabeculectomy; TE(Ologen), TE combined with ologen; TE(AM), TE combined with antimetabolites; GDD, drainage valve implantation; GDD(AM), GDD with antimetabolites; GDD(Ologen), GDD with ologen; GDD(AM+Ologen), GDD(AM) combined with Ologen; TE(AM+Ologen), TE(AM) combined with Ologen; antiVEGF, anti-vascular endothelial growth factor; TE(AM+antiVEGF soaked Ologen), TE(AM) combined with antiVEGF socked Ologen; TE(VTS), TE with viscotrabeculo tomysynechiolysis; TE(C3F8), TE with perfluoropropane; PhacoTE(AM), phacoemulsification combined with TE and AM; PhacoTE(Ologen), phacoemulsification combined with TE and Ologen; PhacoGDD(AM), phacoemulsification combined with GDD and AM; PhacoGDD(AM+Ologen), phacoemulsification combined with GDD, Ologen and antimetabolites; TE(Ologen+GDD), TE(Ologen) combined with GDD). Table 4 Loop-specific approach Loop IF seIF z value p value 95% CI Loop Heterog tau2 IOPR (12 mouth) B-E-F 2.133 11.491 0.186 0.853 (0.00, 24.65) 0.000 Success rate B-E-F 0.124 0.750 0.166 0.868 (0.00, 1.59) 0.000 J-L-M 0.396 0.959 0.413 0.680 (0.00, 2.28) 0.000 J-K-M 0.396 1.083 0.365 0.715 (0.00, 2.52) 0.000 Loop-specific approach is aimed to examine the inconsistency of closed loop. The closer IF is to 0, the better of the direct and indirect evideces' consistency. Note: A=TE(Ologen), B=TE(AM), C=GDD(Ologen), D=GDD, E=TE(AM+Ologen), F=TE(AM+antiVEGF soaked Ologen), G=TE, H=PhacoTE(AM), I=PhacoTE(Ologen), J= GDD(AM+Ologen), K=PhacoGDD(AM), L=PhacoGDD(AM+Ologen), M=GDD(AM), N=TE(VTS), O=TE(C3F8), P=TE(AM+GDD), Q=TE(Ologen+GDD) Table 5 is available in the Supplementary Files section. Additional Declarations The authors declare no competing interests. Supplementary Files Appendixdocument.docx Table2Thecharacteristicsoftheincludedstudies.docx Table5Adverseevents.docx Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-5813928","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Systematic Review","associatedPublications":[],"authors":[{"id":401046662,"identity":"e3ff9d23-f9f5-4226-b8cb-fbde8d092768","order_by":0,"name":"Xi Zhou","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA0UlEQVRIiWNgGAWjYBACNmbmAwckKmx47O8fPkCcFj72tsQHFmfS5BhusCUQp0WO54yxQWXLYWOGGzwGRDpMIsFM4mYDc2Lj7J6PN94w2MnpNhDWkiY5cwdbYrPM2c2WcxiSjc0OENZyTFryDE9iG0PuNmkehgOJ2whrSWyT/tsmkdjDkPOMSC08h5kNJNsMjCUkctiI1MLexvhA4kyCnAHPMWPLOQZE+EW+mf8DMCr/8xiwNz+88abCTo6gFhQgQWzUIGshVccoGAWjYBSMCAAA6LlBn4XBAD0AAAAASUVORK5CYII=","orcid":"","institution":"Hunan Finance and Trade Hospital","correspondingAuthor":true,"prefix":"","firstName":"Xi","middleName":"","lastName":"Zhou","suffix":""}],"badges":[],"createdAt":"2025-01-12 13:47:14","currentVersionCode":1,"declarations":{"humanSubjects":false,"vertebrateSubjects":false,"conflictsOfInterestStatement":false,"humanSubjectEthicalGuidelines":false,"humanSubjectConsent":false,"humanSubjectClinicalTrial":false,"humanSubjectCaseReport":false,"vertebrateSubjectEthicalGuidelines":false},"doi":"10.21203/rs.3.rs-5813928/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-5813928/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":73868164,"identity":"788a7adf-7d2a-43b5-bfb8-d0435ebc2ece","added_by":"auto","created_at":"2025-01-15 12:06:15","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":532397,"visible":true,"origin":"","legend":"\u003cp\u003eLegend not included with this version.\u003c/p\u003e","description":"","filename":"Figure1.LiteratureSearchandScreeningProcess.png","url":"https://assets-eu.researchsquare.com/files/rs-5813928/v1/01eb51929ea3eb28808cfdca.png"},{"id":73868163,"identity":"7f490753-3888-4a0f-ba6f-f9c4e132d575","added_by":"auto","created_at":"2025-01-15 12:06:15","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":104491,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eNetwork of treatment comparisons\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e*Note: The width of the lines is proportional to the number of trials comparing\u003c/p\u003e\n\u003cp\u003eevery pair of treatments. The size of each circle is proportional to the sample size of the intervention. (TE, trabeculectomy; TE(Ologen), TE combined with ologen; TE(AM), TE combined with antimetabolites; GDD, drainage valve implantation; GDD(AM), GDD with antimetabolites; GDD(Ologen), GDD with ologen; GDD(AM+Ologen), GDD(AM) combined with Ologen; TE(AM+Ologen), TE(AM) combined with Ologen; antiVEGF, anti-vascular endothelial growth factor; TE(AM+antiVEGF soaked Ologen), TE(AM) combined with antiVEGF socked Ologen; TE(VTS), TE with viscotrabeculo tomysynechiolysis; TE(C3F8), TE with perfluoropropane; PhacoTE(AM), phacoemulsification combined with TE and AM; PhacoTE(Ologen), phacoemulsification combined with TE and Ologen; PhacoGDD(AM), phacoemulsification combined with GDD and AM; PhacoGDD(AM+Ologen), phacoemulsification combined with GDD, Ologen and antimetabolites; TE(Ologen+GDD), TE(Ologen) combined with GDD).\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-5813928/v1/92bbe870a6930d44435a4103.png"},{"id":73868171,"identity":"c14c8093-8c0f-4a7b-a27b-fe2ee6726fc5","added_by":"auto","created_at":"2025-01-15 12:06:15","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":401084,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eThe results of network meta-analysis\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e*Note: TE, trabeculectomy; TE(Ologen), TE combined with ologen; TE(AM), TE combined with antimetabolites; GDD, drainage valve implantation; GDD(AM), GDD with antimetabolites; GDD(Ologen), GDD with ologen; GDD(AM+Ologen), GDD(AM) combined with Ologen; TE(AM+Ologen), TE(AM) combined with Ologen; antiVEGF, anti-vascular endothelial growth factor; TE(AM+antiVEGF soaked Ologen), TE(AM) combined with antiVEGF socked Ologen; TE(VTS), TE with viscotrabeculo tomysynechiolysis; TE(C3F8), TE with perfluoropropane; PhacoTE(AM), phacoemulsification combined with TE and AM; PhacoTE(Ologen), phacoemulsification combined with TE and Ologen; PhacoGDD(AM), phacoemulsification combined with GDD and AM; PhacoGDD(AM+Ologen), phacoemulsification combined with GDD, Ologen and antimetabolites; TE(Ologen+GDD), TE(Ologen) combined with GDD.\u003c/p\u003e","description":"","filename":"3.png","url":"https://assets-eu.researchsquare.com/files/rs-5813928/v1/3ace9d667f610e3161be2c0a.png"},{"id":73868167,"identity":"3e16a4c5-f989-4bd2-be65-04ca82cfa554","added_by":"auto","created_at":"2025-01-15 12:06:15","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":87157,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eThe funnel plots of each outcome\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e*Note: IOPR, intraocular pressure reduction. (A=TE(Ologen); B=TE(AM); C=GDD(Ologen); D=GDD; E=TE(AM+Ologen); F=TE(AM+antiVEGF soaked Ologen); G=GDD(AM+Ologen); H=GDD(AM); I=TE(VTS); J=TE(C3F8); K=PhacoGDD(AM); L=PhacoGDD(AM+Ologen); M=PhacoTE(AM); N=PhacoTE(Ologen); O=TE; P=TE(AM+Ologen); Q=TE(Ologen+GDD)).\u003c/p\u003e","description":"","filename":"4.png","url":"https://assets-eu.researchsquare.com/files/rs-5813928/v1/0f84ca8825422713aaf20b8e.png"},{"id":73870770,"identity":"2f358707-525c-4366-bc14-105cdec419cb","added_by":"auto","created_at":"2025-01-15 12:22:16","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1902360,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-5813928/v1/25304867-1660-4136-a8f2-346160167c82.pdf"},{"id":73868173,"identity":"6ac1dc73-19c1-48e4-b74c-606a6c34e43a","added_by":"auto","created_at":"2025-01-15 12:06:15","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":5028427,"visible":true,"origin":"","legend":"","description":"","filename":"Appendixdocument.docx","url":"https://assets-eu.researchsquare.com/files/rs-5813928/v1/4af996a65baac127cf7d1d86.docx"},{"id":73870137,"identity":"b7cc1a0f-dc35-4a86-a651-88dab9b20f7b","added_by":"auto","created_at":"2025-01-15 12:14:15","extension":"docx","order_by":2,"title":"","display":"","copyAsset":false,"role":"supplement","size":34202,"visible":true,"origin":"","legend":"","description":"","filename":"Table2Thecharacteristicsoftheincludedstudies.docx","url":"https://assets-eu.researchsquare.com/files/rs-5813928/v1/fab35ca29c916dae76c2485a.docx"},{"id":73868166,"identity":"f2749cf8-6f3b-4100-91c1-2a7ac8c3e595","added_by":"auto","created_at":"2025-01-15 12:06:15","extension":"docx","order_by":3,"title":"","display":"","copyAsset":false,"role":"supplement","size":18675,"visible":true,"origin":"","legend":"","description":"","filename":"Table5Adverseevents.docx","url":"https://assets-eu.researchsquare.com/files/rs-5813928/v1/056fd87189902093b24e6094.docx"}],"financialInterests":"The authors declare no competing interests.","formattedTitle":"\u003cp\u003eShort-term Efficacy and Safety of Ologen Collagen Matrix Implantation for Glaucoma Surgery: A Systematic Review and Network Meta-analysis\u003c/p\u003e","fulltext":[{"header":"Key Point","content":"\u003cp\u003e\u003cstrong\u003eQuestion\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWhat is the best intervention when comparing surgical treatments combined with Ologen and other commonly used surgical treatments for glaucoma?\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFindings\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eIn this network meta-analysis of 2477 patients and 17 treatments, trabeculectomy combined with Ologen and glaucoma drainage device combined with Ologen maybe the best interventions for effectiveness and safety, respectively.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMeaning\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eOlogen combination in treatments for glaucoma patients may improve surgical outcomes. This meta-analysis could guide ophthalmologists in clinical decision making.\u0026nbsp;\u003c/p\u003e"},{"header":"Introduction","content":"\u003cp\u003eGlaucoma is a chronic optic neuropathy characterized by progressive loss of retinal ganglion cells and corresponding visual field defects. It is one of the leading causes of irreversible blindness worldwide, affecting more than 70\u0026nbsp;million people\u003csup\u003e\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u003c/sup\u003e. Glaucoma can be classified into four general categories: primary open-angle and angle-closure, and secondary open and angle-closure glaucoma. The most common type in the United States is primary open-angle glaucoma\u003csup\u003e\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eThe main risk factor for glaucoma is elevated intraocular pressure (IOP), which can damage the optic nerve and impair its function\u003csup\u003e\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u003c/sup\u003e. Elevated IOP is the crucial determinant of disease progression, which remains the only modifiable risk factor. Therefore, all current treatments for glaucoma aim to lower the IOP by various methods, such as medications, lasers, and surgeries\u003csup\u003e\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eAmong the surgical options, trabeculectomy and aqueous shunt devices are commonly used for advanced glaucoma that is refractory to medical or laser therapy. Trabeculectomy, first introduced by Cairns in 1968, has been considered the gold standard for glaucoma surgery, as it can achieve low and stable IOP levels\u003csup\u003e\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e,\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u003c/sup\u003e. However, trabeculectomy has a variable success rate ranging from 11\u0026ndash;52%, depending on the definition of success and the follow-up duration. Moreover, trabeculectomy is associated with several complications, such as infection, hypotony, bleb leakage, and cataract\u003csup\u003e\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e,\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u003c/sup\u003e. To improve the outcome and safety of trabeculectomy, antimetabolites such as mitomycin C and 5-fluorouracil have been used as adjunctive agents in the intraoperative and postoperative periods. This modified trabeculectomy has become a new trend in the clinical treatment of glaucoma\u003csup\u003e\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eGlaucoma drainage implant surgeries have become more popular for the treatment of glaucoma in recent years\u003csup\u003e\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e,\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e\u003c/sup\u003e, especially for refractory cases that fail to respond to medical or laser therapy or previous trabeculectomy\u003csup\u003e\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u003c/sup\u003e. Glaucoma drainage implant surgeries can lower intraocular pressure by diverting aqueous humor from the anterior chamber to a plate or tube that is implanted in the subconjunctival or sub-Tenon space.\u003c/p\u003e \u003cp\u003eCompared with trabeculectomy, glaucoma drainage implant surgeries have some advantages, such as less dependence on the conjunctival wound healing process, less risk of hypotony or bleb-related complications, and more predictable intraocular pressure control. However, glaucoma drainage implant surgeries also have some disadvantages, such as higher cost, longer surgical time, higher risk of tube erosion or infection, and lower success rate in some types of glaucoma\u003csup\u003e\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e,\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e\u003c/sup\u003e. According to some studies, the rate of choosing GDIs for resurgical treatment of glaucoma was 9%, while the rate of choosing modified trabeculectomy with antimetabolites was 29%\u003csup\u003e13\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eA meta-analysis of clinical studies comparing drainage implant surgeries and other operations found no significant difference between drainage valve implantation and trabeculectomy in reducing IOP, postoperative antiglaucoma medications, and success rate. However, drainage valve surgery had significantly fewer postoperative complications and faster recovery of visual acuity than trabeculectomy\u003csup\u003e\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e,\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e\u003c/sup\u003e. On the other hand, drainage implant surgeries were more expensive than trabeculectomy, and imposed a greater financial burden on most patients\u003csup\u003e\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u003c/sup\u003e. Therefore, it is important to select the appropriate surgical method according to the patients\u0026rsquo; individual characteristics.\u003c/p\u003e \u003cp\u003eOlogen collagen matrix is a novel biomaterial for glaucoma surgery. It is a degradable, porous, collagen-glycosaminoglycan scaffold that is placed between the conjunctiva and episcleral space to modulate wound healing and reduce scar formation. By doing so, it lowers the resistance to the aqueous humor outflow and maintains the filtration function\u003csup\u003e\u003cspan additionalcitationids=\"CR17\" citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e\u003c/sup\u003e. Ologen collagen matrix affects the cellular and molecular events during wound healing, such as the reorganization of myofibroblasts, fibroblasts, and extracellular matrix. The collagen density and structure in Ologen-treated wounds resemble those of normal conjunctival connective tissue\u003csup\u003e\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e,\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e,\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eOlogen can be used as an adjunctive material in various glaucoma surgical procedures. For example, Ologen matrix with drainage valve implantation, Ologen-augmented trabeculectomy. As phacoemulsification is often combined with drainage valve implantation, which results in significant IOP reduction in the combined procedure\u003csup\u003e\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e\u003c/sup\u003e. Moreover, lens extraction itself also affects postoperative IOP measurement\u003csup\u003e\u003cspan additionalcitationids=\"CR22\" citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e\u003c/sup\u003e. Therefore, whether combined with phacoemulsification or not is also worth discussing as an independent variable.\u003c/p\u003e \u003cp\u003eThe purpose of this network meta-analysis was to compare the efficacy and safety of commonly used interventions with or without ologen in patients with glaucoma.\u003c/p\u003e"},{"header":"Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eData sources\u003c/h2\u003e \u003cp\u003eWe searched Pubmed, Embase, Web of science and Cochrane for studies on the effect of glaucoma surgery with or without ologen, such as ologen-augmented trabeculectomy, drainage valve implantation with ologen insertion, etc. from their inception through January 1, 2023. We did not apply any restrictions on publication year, language or study design. We used medical subject headings and keywords, including \u0026lsquo;glaucoma\u0026rsquo;, \u0026lsquo;collagen-glycosaminoglycan copolymer\u0026rsquo; and \u0026lsquo;ologen\u0026rsquo;, etc. The details of the search strategy are shown in appendix 1 to 4. Two investigators independently screened the titles and abstracts of the retrieved studies. We contacted the corresponding authors if missing critical data were found. We applied the inclusion and exclusion criteria to the full texts of the selected studies. A third investigator carefully checked the final included studies.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eStudy selection\u003c/h3\u003e\n\u003cp\u003eWe included studies that met the following criteria: (1) study type: randomised controlled trials (RCTs) or cohort studies; (2) population: patients with glaucoma, whether primary or secondary, open-angle or closed-angle; (3) intervention: comparison of the postoperative effect of different glaucoma surgeries combined with ologen with a control group. (4) outcome variables: availability of at least one of the outcome measures; (5) connection: inclusion of some appropriate studies to maintain the connection of the network during comparison.\u003c/p\u003e \u003cp\u003eWe excluded studies that had one of the following conditions: (1) follow-up time of \u0026lt;\u0026thinsp;6 months; (2) small sample size with n\u0026thinsp;\u0026lt;\u0026thinsp;5; (3) the same surgical method or its modified version in both groups without considering the addition of ologen, for example, a study of drainage valve implantation versus drainage implant surgeries with mitomycin was excluded; (4) drug dose related studies; (5) studies without the required data and the data could not be obtained by contacting the corresponding author, or the corresponding author was unreachable.\u003c/p\u003e\n\u003ch3\u003eOutcomes\u003c/h3\u003e\n\u003cp\u003eThe primary outcome was the mean difference of IOPR (intraocular pressure reduction) after surgery, regardless of whether antiglaucoma medication was used or not. The required data were calculated by the following formula if the mean difference and standard deviation (SD) of IOPR were not provided by the authors\u003csup\u003e\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e,\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e\u003c/sup\u003e: IOPR\u0026thinsp;=\u0026thinsp;IOP\u003csub\u003ebaseline\u003c/sub\u003e \u0026ndash; IOP\u003csub\u003eendpoint\u003c/sub\u003e, SD\u003csub\u003eIOPR\u003c/sub\u003e = SD\u003csub\u003ebaseline\u003c/sub\u003e\u003csup\u003e2\u003c/sup\u003e + SD\u003csub\u003eendpoint\u003c/sub\u003e\u003csup\u003e2\u003c/sup\u003e \u0026ndash; (2 \u0026times; SD\u003csub\u003ebaseline\u003c/sub\u003e \u0026times; SD\u003csub\u003eendpoint\u003c/sub\u003e)\u003csup\u003e1/2\u003c/sup\u003e. We extracted the IOP data at 12 months after surgery from the included studies to reduce bias. If the IOP data at 12 months postoperative were not reported, then the study was excluded from the analysis of IOPR outcome.\u003c/p\u003e \u003cp\u003eThe secondary outcome was success rate. If there was no common time point reporting the success rate among included studies, we used the success rate of the final follow-up.\u003c/p\u003e\n\u003ch3\u003eData Extraction\u003c/h3\u003e\n\u003cp\u003eTwo investigators independently extracted the following data from the included studies: (1) demographic data, such as authors\u0026rsquo; name, study design, publication year, patients\u0026rsquo; age and gender, sample size of discussion group, primary cause of glaucoma and follow-up time; (2) outcome data, such as IOPR at 12 months postoperatively and success rate at the end of follow-up.\u003c/p\u003e\n\u003ch3\u003eQuality assessment\u003c/h3\u003e\n\u003cp\u003eWe used the Cochrane risk of bias tool and the Newcastle-Ottawa scale to assess the quality of randomized/non-randomized controlled trials and retrospective cohort studies, respectively. Two investigators independently performed the quality assessment, and resolved any disagreement by consensus with all investigators.\u003c/p\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eData Synthesis\u003c/h2\u003e \u003cp\u003eThis network meta-analysis was executed through Stata (Version 17.0). Treatments that compared the surgical effect of ologen and other methods were comprised in this meta-analysis. This meta-analysis was using two indicators, the IOPR at 12 mouth after surgery and success rate to assess the effect of different treating methods. Mean difference and 95% credible interval (CI) were used to analyze the continuous variable, while dichotomous variables using odds ratio (OR).\u003c/p\u003e \u003cp\u003eWe prepared the network analysis data using the \u0026lsquo;network setup\u0026rsquo; command. We drew the network forest and network map using the \u0026lsquo;network forest\u0026rsquo; and \u0026lsquo;network map\u0026rsquo; commands. We checked the local inconsistency by node splitting and loop-specific approaches. We assessed the heterogeneity of included studies using I\u003csup\u003e\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u003c/sup\u003e and χ\u003csup\u003e\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u003c/sup\u003e statistics and considered it significant if I\u003csup\u003e\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u003c/sup\u003e was \u0026gt;\u0026thinsp;50% or the P value\u0026thinsp;\u0026lt;\u0026thinsp;0.05\u003csup\u003e26,27\u003c/sup\u003e. We used the 'Mvmeta\u0026rsquo; package to perform the plots of different comparisons, the rankplots based on probabilities and the surface under the cumulative ranking (SUCRA) for different endpoints. We used the Grades of Recommendations Assessment, Development and Evaluation to assess the quality of the outcomes\u003csup\u003e\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eStrength of Evidence\u003c/h3\u003e\n\u003cp\u003eThe strength of evidence was assessed by using Grade of Recommendations Assessment, Development and Evaluation (GRADE). Ratings were based on heterogeneity (low, some and major), within-study bias (low, some and major), incoherence (low, some and major), indirectness (low, some and major), imprecision (low, some and major), and reporting bias (suspected or undetected). The strength of evidence was assigned an overall grade of high, moderate, low, or very low by evaluating and weighing the combined results of the above domains\u003csup\u003e\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e\u003c/sup\u003e. Grades were initially assessed by 1 investigator and then reviewed by all investigators for consensus.\u003c/p\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003eIdentification of the relevant studies\u003c/h2\u003e \u003cp\u003eWe initially searched for 452 articles discussing the effect of Ologen. We excluded 141 articles for duplications, 177 articles by title, and 18 articles by abstracts. We checked the full texts of the remaining articles for eligibility. We excluded 11 articles for being case reports, 16 articles for having inappropriate controls, 18 articles for being non-human research, and 16 articles for being reviews, meta-analyses, letters or conferences. We excluded 23 articles for having unavailable or improper data. We included 32 articles in the final screening (Appendix 5 shows the reference list of screened studies). We added three studies to connect the network of this meta-analysis. We included 35 studies in the final analysis. Figure\u0026nbsp;1 shows the selection procedure and the details of the added studies.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec12\" class=\"Section2\"\u003e \u003ch2\u003eCharacteristics of the included studies\u003c/h2\u003e \u003cp\u003eThis network meta-analysis included 2477 patients. The sample size for each group ranged from 8 to 107. The included studies consisted of 18 randomized controlled trials, 4 non-randomized prospective trials and 13 retrospective cohort studies. There were 31 two-arm studies and 4 three-arm studies in total.\u003c/p\u003e \u003cp\u003eFor the outcome of IOPR at 12 months postoperatively, we included 10 surgical treatments in 19 studies. The surgical treatments were: trabeculectomy (TE) with ologen (TE(Ologen)), TE with antimetabolites (TE(AM)), drainage valve implantation (GDD), GDD with antimetabolites (GDD(AM)), GDD with ologen (GDD(Ologen)), GDD(AM) and ologen (GDD(AM\u0026thinsp;+\u0026thinsp;Ologen)), TE(AM) and ologen (TE(AM\u0026thinsp;+\u0026thinsp;Ologen)), TE(AM) and anti-vascular endothelial growth factor (antiVEGF) soaked ologen (TE(AM\u0026thinsp;+\u0026thinsp;antiVEGF soaked Ologen)), TE with viscotrabeculotomy-synechiolysis (TE(VTS)) and TE with perfluoropropane (TE(C3F8)).\u003c/p\u003e \u003cp\u003eFor the outcome of success rate, we included 17 surgical interventions in 31 studies. The surgical interventions were: TE, TE(Ologen), TE(AM), GDD, GDD(AM), GDD(Ologen), GDD(AM\u0026thinsp;+\u0026thinsp;Ologen), TE(AM\u0026thinsp;+\u0026thinsp;Ologen), TE(AM\u0026thinsp;+\u0026thinsp;antiVEGF soaked Ologen), TE(VTS), TE(C3F8), phacoemulsification with TE and AM (phacoTE(AM)), phacoTE with Ologen (phacoTE(Ologen)), phacoemulsification with GDD and AM (phacoGDD(AM)), phacoGDD with Ologen and antimetabolites (phacoGDD(AM\u0026thinsp;+\u0026thinsp;Ologen)), TE(AM) and GDD (TE(AM\u0026thinsp;+\u0026thinsp;GDD)) and TE(Ologen) and GDD (TE(Ologen\u0026thinsp;+\u0026thinsp;GDD)). Table\u0026nbsp;1 shows the definitions of the acronyms.\u003c/p\u003e \u003cp\u003eFor the outcome of IOPR at 12 months after surgery, we included 19 studies. The comparisons were: TE(Ologen) vs TE(AM) (10 studies), TE(AM) vs GDD(AM) (1 study), TE(AM\u0026thinsp;+\u0026thinsp;Ologen) vs TE(AM)\u0026thinsp;+\u0026thinsp;anti-VEGF soaked Ologen (1 study), TE(Ologen) vs TE(C3F8) (1 study), TE(AM) vs TE(AM\u0026thinsp;+\u0026thinsp;Ologen) (3 studies), GDD(Ologen) vs GDD(AM\u0026thinsp;+\u0026thinsp;Ologen) (1 study), GDD(AM\u0026thinsp;+\u0026thinsp;Ologen) vs GDD(AM) (1 study), TE(Ologen) vs TE(VTS) (1 study), TE(AM) vs TE(AM\u0026thinsp;+\u0026thinsp;antiVEGF soaked Ologen) (1 study), GDD vs GDD(Ologen) (2 studies), and GDD(Ologen) vs GDD(AM) (1 study).\u003c/p\u003e \u003cp\u003eFor the outcome of success rate, we included 31 studies. The comparisons were: TE(Ologen) vs TE(AM) (8 studies), TE(Ologen) vs TE(VTS) (1 study), TE(AM) vs phacoTE(AM) (1 study), phacoGDD(AM) vs GDD(AM\u0026thinsp;+\u0026thinsp;Ologen) (1 study), phacoGDD(AM\u0026thinsp;+\u0026thinsp;Ologen) vs GDD(AM) (1 study), TE(Ologen) vs TE(C3F8) (1 study), TE(AM) vs GDD(AM) (1 study), GDD(AM\u0026thinsp;+\u0026thinsp;Ologen) vs phacoGDD(AM\u0026thinsp;+\u0026thinsp;Ologen) (1 study), GDD(AM\u0026thinsp;+\u0026thinsp;Ologen) vs GDD(AM) (3 studies), TE(AM\u0026thinsp;+\u0026thinsp;GVI) vs TE(Ologen\u0026thinsp;+\u0026thinsp;GDD) (1 study), TE(Ologen) vs TE (1 study), TE(AM) vs TE(AM\u0026thinsp;+\u0026thinsp;Ologen) (3 studies), TE(AM) vs TE(AM\u0026thinsp;+\u0026thinsp;antiVEGF soaked Ologen) (1 study), TE(AM\u0026thinsp;+\u0026thinsp;GVI) vs TE(AM\u0026thinsp;+\u0026thinsp;Ologen) (1 study), GDD(AM) vs phaco GDD(AM) (1 study), GDD(Ologen) vs GDD (5 studies), TE(AM\u0026thinsp;+\u0026thinsp;Ologen) vs TE(AM\u0026thinsp;+\u0026thinsp;antiVEGF soaked Ologen) (1 study), phacoTE(AM) vs phacoTE(Ologen) (4 studies), phacoGVI (AM) vs phacoGDD(Ologen\u0026thinsp;+\u0026thinsp;AM) (1 study), and TE(AM) vs GDD (1 study).\u003c/p\u003e \u003cp\u003eThe number of patients in different surgical treatment groups varied by the outcome of IOPR at 12 months after surgery. The groups were: TE(Ologen) (278 patients), TE(AM) (410 patients), GDD(Ologen) (38 patients), GDD (29 patients), TE(AM\u0026thinsp;+\u0026thinsp;Ologen) (90 patients), TE(AM\u0026thinsp;+\u0026thinsp;antiVEGF soaked Ologen) (44 patients), GDD(AM\u0026thinsp;+\u0026thinsp;Ologen) (6 patients), GDD(AM) (101 patients), TE(VTS) (22 patients) and TE(C3F8) (28 patients).\u003c/p\u003e \u003cp\u003eThe total number of patients included for the outcome of success rate in different surgical treatments were: TE(Ologen) (256 patients), TE(AM) (596 patients), GDD(Ologen) (89 patients), GDD (278 patients), TE(AM\u0026thinsp;+\u0026thinsp;Ologen) (154 patients), TE(AM\u0026thinsp;+\u0026thinsp;antiVEGF soaked Ologen) (46 patients), TE (20 patients), phacoTE(AM) (200 patients), phacoTE(Ologen) (118 patients), GDD(AM\u0026thinsp;+\u0026thinsp;Ologen) (90 patients), phacoGDD(AM) (12 patients), phacoGDD(AM\u0026thinsp;+\u0026thinsp;Ologen) (19 patients), GDD(AM) (176 patients), TE(VTS) (24 patients), TE(C3F8) (28 patients), TE(AM\u0026thinsp;+\u0026thinsp;GVI) (70 patients), and TE(Ologen\u0026thinsp;+\u0026thinsp;GDD) (49 patients).\u003c/p\u003e \u003cp\u003eThe success criteria for the 35 studies were defined by the authors and are summarized in Appendix 6. The demographic characteristics of each study are shown in Table\u0026nbsp;2.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec13\" class=\"Section2\"\u003e \u003ch2\u003eQuality assessment\u003c/h2\u003e \u003cp\u003eOf the 18 randomized clinical trials (RCTs), 6 used computer-generated random numbers and 5 did not report the randomization method. The other 7 RCTs used various methods, such as drawing lots, coin flipping, sealed envelopes, consort guidelines, permuted block randomization, randomized blocks design, and single-and-even number randomization. Only 3 RCTs reported the blinding method and 2 reported non-blinding. The rest did not mention blinding in the full text. Fourteen RCTs provided complete outcome data and 4 provided incomplete data. The risk of bias summary for all RCTs is shown in appendix 7.\u003c/p\u003e \u003cp\u003eThe quality of the 13 included retrospective cohort studies was assessed using the Newcastle-Ottawa Quality Assessment Scale. Three studies scored 8 points, 7 scored 7 points, and 3 scored 6 points (Appendix 8). The quality of the 4 non-randomized studies was evaluated using the Methodological Index for Non-randomized Studies, and all scored higher than 16 points\u003csup\u003e\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e\u003c/sup\u003e. Details are shown in Appendix 9.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec14\" class=\"Section2\"\u003e \u003ch2\u003eThe results of meta-analysis\u003c/h2\u003e \u003cp\u003eThe network plots for success rate and IOPR at 12 months postoperative are shown in Fig.\u0026nbsp;2. The forest plots are shown in Fig.\u0026nbsp;3. The results of pairwise meta-analysis of IOPR at 12 months and success rate are presented in appendix 10.\u003c/p\u003e \u003cp\u003eNineteen studies involving 1046 eyes are included in the discussion of IOPR at 12 mouth postoperatively (Fig.\u0026nbsp;2). However, no statistically significant difference was found when comparing TE(Ologen) and other interventions.\u003c/p\u003e \u003cp\u003eThe success rate was assessed for 2191 eyes from 31 studies involving 17 interventions. The network forest plots are shown in Fig.\u0026nbsp;3. Compared with TE(Ologen), PhacoGDD(AM) (OR, -0.75; 95% CI, -2.20 to 0.70), TE(C3F8) (OR, -0.64; 95% CI, -2.08 to 0.79), TE(AM\u0026thinsp;+\u0026thinsp;GDD) (OR, -0.95; 95% CI, -2.65 to 0.76), and TE(Ologen\u0026thinsp;+\u0026thinsp;GDD) (OR, 0.07; 95% CI, -0.81 to 0.96) showed significant differences. Compared with TE(AM\u0026thinsp;+\u0026thinsp;antiVEGF soaked Ologen), TE (OR, -0.49; 95% CI, -1.88 to 0.90), PhacoTE(Ologen) (OR, -0.34; 95% CI, -1.25 to 0.57), PhacoGDD(AM) (OR, -1.92; 95% CI, -4.67 to 0.83), TE(C3F8) (OR, -1.81; 95% CI, -4.55 to 0.93), and TE(AM\u0026thinsp;+\u0026thinsp;GDD) (OR, -2.12; 95% CI, -5.02 to 0.78) showed significant differences. Compared with GDD(AM), TE(VTS) (OR, -0.26; 95% CI, -1.46 to 0.94), TE(C3F8) (OR, -1.13; 95% CI, -2.78 to 0.52), TE(AM\u0026thinsp;+\u0026thinsp;GDD) (OR, -1.43; 95% CI, -3.33 to 0.46), and TE(Ologen\u0026thinsp;+\u0026thinsp;GDD) (OR, -0.41; 95% CI, -1.61 to 0.79) showed significant differences. Compared with TE(VTS), TE(C3F8) (OR, -0.87; 95% CI, -2.25 to 0.51), TE(AM\u0026thinsp;+\u0026thinsp;GDD) (OR, -1.17; 95% CI, -2.84 to 0.49), and TE(Ologen\u0026thinsp;+\u0026thinsp;GDD) (OR, -0.16; 95% CI, -0.94 to 0.63) showed significant differences. A significant difference was also found between TE(C3F8) and TE(AM\u0026thinsp;+\u0026thinsp;GDD) (OR, -0.31; 95% CI, -1.24 to 0.63) and between GDD(AM\u0026thinsp;+\u0026thinsp;Ologen) and PhacoGDD(AM) (OR, -0.26; 95% CI, -1.40 to 0.87). No significant difference was found between any other two interventions. Details are shown in Appendix 10.\u003c/p\u003e \u003cp\u003eThe probability ranking plot and the SUCRA are shown in Appendix 11. Table\u0026nbsp;3 shows the specific ranking for each intervention for success rate and IOPR. For IOPR at 12 months postoperatively, TE(Ologen) had the highest probability of being the best among the 10 interventions, followed by TE, TE(C3F8), and TE(VTS). GDD(Ologen) was the best intervention for success rate, while PhacoTE(AM), GDD, and PhacoTE(Ologen) ranked lower, respectively.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec15\" class=\"Section2\"\u003e \u003ch2\u003eConsistency analysis\u003c/h2\u003e \u003cp\u003eThe inconsistency was assessed by node-splitting analysis, which compared direct and indirect effects (Appendix 12). No significant inconsistency was found, indicating that the results were reliable. The loop-specific analysis showed that the comparisons of closed circles for success rate had no significant inconsistency, but the loop-specific analysis for IOPR showed inconsistency between direct and indirect comparisons (Table\u0026nbsp;4).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec16\" class=\"Section2\"\u003e \u003ch2\u003eGrade of Recommendations Assessment, Development and Evaluation (GRADE) for the outcome measurements\u003c/h2\u003e \u003cp\u003eThe specific details of the GRADE evaluation for success rate and IOPR are shown in Appendix 13 and Appendix 14, respectively. The evaluation of direct comparison in network meta-analysis was similar to that of meta-analysis, and the indirect comparison used the lowest score among the included direct comparisons as its evaluation level. As a result, the evidence included in this network meta-analysis was of moderate, low, or very low quality.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec17\" class=\"Section2\"\u003e \u003ch2\u003eComplications\u003c/h2\u003e \u003cp\u003ePostoperative complications were reported in 31 of the 35 included studies. Twenty-one studies reported 94 cases of postoperative low intraocular pressure, with the following distribution: TE(Ologen), 15 cases; TE(AM), 31 cases; GDD(Ologen), 6 cases; GDD, 4 cases; TE(AM\u0026thinsp;+\u0026thinsp;Ologen), 5 cases; TE(AM\u0026thinsp;+\u0026thinsp;anti-VEGF soaked Ologen), 2 cases; TE, 1 case; PhacoTE(AM), 7 cases; PhacoTE(Ologen), 3 cases; GDD(AM\u0026thinsp;+\u0026thinsp;Ologen), 8 cases; GDD(AM), 11 cases; and TE(C3F8), 1 case.\u003c/p\u003e \u003cp\u003eBleb leak was reported in 30 studies, with 43 cases in total. The distribution of cases was as follows: GDD and TE(AM\u0026thinsp;+\u0026thinsp;Ologen), 1 case each; GDD(Ologen), TE(AM\u0026thinsp;+\u0026thinsp;anti-VEGF soaked Ologen), and PhacoTE(Ologen), 3 cases each; TE(Ologen), 2 cases; TE(AM), 13 cases; TE(GDD\u0026thinsp;+\u0026thinsp;AM), 9 cases; and TE(GDD\u0026thinsp;+\u0026thinsp;Ologen), 8 cases.\u003c/p\u003e \u003cp\u003eBleb failure was reported in 11 studies, with 69 cases in total. The distribution of cases was as follows: GDD(Ologen), GDD, and PhacoTE(Ologen), 6 cases each; GDD(AM\u0026thinsp;+\u0026thinsp;Ologen) and TE(GDD\u0026thinsp;+\u0026thinsp;AM), 1 case each; TE(AM\u0026thinsp;+\u0026thinsp;Ologen) and PhacoTE(AM), 2 cases each; TE(Ologen), 11 cases; TE(AM), 8 cases; TE, 5 cases; GDD(AM), 18 cases; and TE(C3F8), 3 cases.\u003c/p\u003e \u003cp\u003eTube-associated complications, such as tube obstruction, tube exposure, and tube migration, were reported in 3 studies. There were 5 cases each in the GDD(Ologen) and GDD groups. Postoperative intraocular hypertension was reported in 3 studies, with the following distribution of cases: TE(AM), 14 cases; GDD(Ologen), 7 cases; GDD, 14 cases; and GDD(AM), 13 cases. One case of phthisis bulbi in the GDD group was reported in 1 study.\u003c/p\u003e \u003cp\u003eSignificant loss of vision after surgery was reported in 4 studies. The distribution of cases was as follows: TE(Ologen), GDD, and PhacoTE(AM), 4 cases each; TE(AM), 5 cases; and GDD(Ologen), 3 cases. Corneal edema was reported in 3 studies, with 6 cases in total. The distribution of cases was as follows: GDD(Ologen), 2 cases; GDD, 3 cases; and GDD(AM\u0026thinsp;+\u0026thinsp;Ologen), 1 case.\u003c/p\u003e \u003cp\u003eShallow anterior chamber was reported in 16 studies, with 59 cases in total. The distribution of cases was as follows: TE, PhacoTE(AM), PhacoTE(Ologen), TE(VTS), and TE(C3F8), 1 case each; GDD(Ologen), GDD, and TE(GDD\u0026thinsp;+\u0026thinsp;AM), 4 cases each; TE(Ologen), 18 cases; TE(AM\u0026thinsp;+\u0026thinsp;Ologen), 8 cases; and TE(AM), 18 cases.\u003c/p\u003e \u003cp\u003eAnterior chamber exudation was reported in 4 studies, with 31 cases in total. The distribution of cases was as follows: TE(Ologen) and TE(AM), 12 cases each; PhacoTE(AM), 2 cases; and PhacoTE(Ologen), 5 cases. Hyphema was reported in 30 studies, with 45 cases in total. The distribution of cases was as follows: TE(AM\u0026thinsp;+\u0026thinsp;Ologen), TE(AM\u0026thinsp;+\u0026thinsp;anti-VEGF soaked Ologen), and TE, 3 cases each; TE(AM), 10 cases; GDD(Ologen), 6 cases; GDD, 4 cases; TE(VTS), 2 cases; and TE(GDD\u0026thinsp;+\u0026thinsp;AM), 1 case.\u003c/p\u003e \u003cp\u003eVitreous hemorrhage was reported in 2 studies, with 3 cases in total. There was 1 case each in the TE(AM\u0026thinsp;+\u0026thinsp;anti-VEGF soaked Ologen), TE(AM\u0026thinsp;+\u0026thinsp;Ologen), and GDD groups. Choroidal detachment was reported in 15 studies, with 51 cases in total. The distribution of cases was as follows: GDD, PhacoTE(AM), and PhacoTE(Ologen), 4 cases each; TE(GDD\u0026thinsp;+\u0026thinsp;AM) and TE(GDD\u0026thinsp;+\u0026thinsp;Ologen), 2 cases each; TE(Ologen) and TE(AM\u0026thinsp;+\u0026thinsp;Ologen), 8 cases each; TE(AM), 14 cases; and GDD(Ologen), 5 cases. Retinal detachment was reported in 1 study, with 1 case in the GDD group.\u003c/p\u003e \u003cp\u003eTwo studies reported a total of eight cases of glaucoma recurrence, with 1, 2, 3, and 2 cases in the GDD(Ologen), PhacoGDD(AM\u0026thinsp;+\u0026thinsp;Ologen), GDD(AM\u0026thinsp;+\u0026thinsp;Ologen), and GDD(AM) groups, respectively. In addition to the commonly seen postoperative complications described above, a total of 23 studies reported 201 other cases. These included six cases each in the TE(AM\u0026thinsp;+\u0026thinsp;anti-VEGF soaked Ologen), GDD(AM\u0026thinsp;+\u0026thinsp;Ologen), and GDD(AM) groups; five cases each in the PhacoTE(Ologen) and TE(GDD\u0026thinsp;+\u0026thinsp;AM) groups; 25 cases in the TE(Ologen) group; 69 cases in the TE(AM) group; 12 cases in the GDD(Ologen) group; 20 cases in the GDD group; 33 cases in the TE(AM\u0026thinsp;+\u0026thinsp;Ologen) group; three cases in the PhacoTE(AM) group; nine cases in the TE(VTS) group; and two cases in the TE(C3F8) group. Further details are presented in Appendix 15.\u003c/p\u003e \u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eThis is the first meta-analysis to evaluate the safety and efficacy of Ologen compared to other commonly used treatments in glaucoma patients. The aim of this study was to explore more effective treatment options.\u003c/p\u003e \u003cp\u003eUntil now, there have been relatively few meta-analyses concerning Ologen and other interventions, and no network meta-analyses. The most recent meta-analysis, conducted in 2019 by Song et al., compared the efficacy of Ologen and mitomycin in trabeculectomy. The study concluded that trabeculectomy with mitomycin was associated with higher IOP-lowering efficacy, but also a higher incidence of post-surgery complications compared to trabeculectomy with Ologen\u003csup\u003e\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e\u003c/sup\u003e. Although there have been several clinical studies comparing the efficacy of Ologen with other treatments, a network meta-analysis comparing Ologen and other commonly used treatments in glaucoma patients is still lacking. It is necessary to conduct such a network meta-analysis to compare the use of Ologen collagen matrix with other interventions in glaucoma patients.\u003c/p\u003e \u003cp\u003eThe results of our analysis suggest that GDD(Ologen) was the most effective intervention in terms of surgical success rate, followed by PhacoTE(AM), with TE ranked last. In terms of IOP reduction at 12 months postoperatively, TE(Ologen) was the most effective intervention, followed by TE(AM). GDD(Ologen), GDD and GDD(AM) were ranked in the bottom three.\u003c/p\u003e \u003cp\u003eThere are three possible reasons for the discrepancy between the best and worst rankings for IOPR and surgical success rate. First, the inconsistency in follow-up times for the two surgical outcomes among the studies may have contributed to the discrepancy. To avoid bias, only IOP measurements at 12 months postoperatively were included. However, the time point for reporting surgical success rate varied among studies. Although there is insufficient information to conclude whether there are differences between glaucoma drainage device implantation and trabeculectomy for glaucoma treatment, aqueous shunt implantation is considered to be a lower-risk option with a lower risk of failure and is a more favorable choice among surgeons\u003csup\u003e\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e,\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e\u003c/sup\u003e. As follow-up time increases, fibrosis of the conjunctiva and scarring in trabeculectomy can affect the surgical success rate\u003csup\u003e\u003cspan additionalcitationids=\"CR34\" citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eSecondly, differences in the data from studies and interventions included in the discussions of IOP reduction and surgical success rate may also contribute to the discrepancy. For IOP reduction, 19 studies and 10 interventions were included, while for surgical success rate, 31 studies and 17 interventions were included. This study did not categorize different glaucoma drainage devices because there is currently no evidence to support the superiority of one device over another\u003csup\u003e\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e,\u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e,\u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eLastly, asymmetry in the funnel plots for surgical success rate and IOPR suggests the presence of potential bias (Fig.\u0026nbsp;4). The loop-specific analysis of IOPR showed probable inconsistency between direct and indirect comparisons (Table\u0026nbsp;4). Therefore, the result that GDD(Ologen) ranked at the bottom of the IOPR list should be interpreted with caution.\u003c/p\u003e \u003cp\u003eIn summary, the adverse events reported in this meta-analysis are shown in Table\u0026nbsp;5. First, low IOP, bleb leak, significant loss of vision during follow-up, and choroidal detachment were more commonly seen in the TE(AM) group. Second, tube-associated complications such as tube obstruction, tube exposure, and tube migration were more frequently reported in the GDD(Ologen) and GDD groups. Third, shallow anterior chamber, anterior chamber exudation, and hyphema were more frequently reported in the TE(Ologen) group. Fourth, vitreous hemorrhage was only reported in the GDD, TE(AM\u0026thinsp;+\u0026thinsp;Ologen) and TE(AM\u0026thinsp;+\u0026thinsp;antiVEGF soaked Ologen) group among the 17 interventions. Fifth, low IOP was the most common complication in the TE(Ologen) and TE(AM) groups. Sixth, postoperative intraocular hypertension was the most common complication in the GDD(Ologen) and GDD groups. Seventh, no complications were reported in the PhacoGDD(AM) group. Although the number of complications is relatively small, their incidence varied greatly among groups. Additionally, the complications reported by each study varied, so the results should be interpreted with caution. Finally, the number of patients with complications was concentrated in the TE(Ologen), TE(AM), GDD(Ologen), GDD and TE(AM\u0026thinsp;+\u0026thinsp;Ologen) groups. This may be due to most of the included studies performing pairwise analysis between these interventions.\u003c/p\u003e \u003cp\u003eThis study has several advantages. First, it is the first network meta-analysis to compare different interventions with or without Ologen. The direct and indirect effects of 17 treatments were compared, and a SUCRA plot was generated to evaluate the rankings of the included interventions. Additionally, the heterogeneity among the evidence was relatively low, making the results more reliable and useful for ophthalmologists when deciding on the most appropriate surgical treatment for glaucoma patients.\u003c/p\u003e \u003cp\u003eHowever, there are also several limitations to this study. First, the GRADE rating for outcome measurements was relatively low, with no high-scored measurements and several very low ratings. Second, the loop-specific analysis of IOP reduction showed inconsistency between direct and indirect comparisons. Third, the interventions discussed for IOPR and surgical success rate were not consistent, with 10 and 17 interventions included, respectively. This inconsistency in the number of interventions may introduce potential bias between the analysis results for the two surgical outcomes. Fourth, the criteria for defining surgical success varied among studies, which could be another source of research bias.\u003c/p\u003e \u003cp\u003eFifth, the number of studies analyzing different intervention groups varied considerably. For example, 13 studies discussed the TE(Ologen) group, while only one study referred to the TE(AM\u0026thinsp;+\u0026thinsp;anti-VEGF soaked Ologen) group. Sixth, the number of outcomes discussed in this network meta-analysis was limited. Only IOPR at 12 months and surgical success rate were included due to the limited categories of postoperative follow-up examinations and data reported in the included studies. If more types of surgical outcomes were included, the reliability of this network meta-analysis would be higher. For instance, differences in best-corrected visual acuity, perimetry results, and glaucoma medication use pre- and postoperatively could also be considered when analyzing different interventions.\u003c/p\u003e \u003cp\u003eSeventh, the composition of primary diseases in the included studies was inconsistent. These differences may influence the efficacy of surgery and introduce potential bias. Finally, the number of RCTs was relatively low. This meta-analysis included three types of studies due to the limited number of eligible studies: 18 RCTs, 17 retrospective studies, and 3 non-randomized prospective studies. Some interventions were not included due to a limited number of studies. These limitations may affect the final outcomes and could be improved in future research with more refined study design.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eIn conclusion, this network meta-analysis found that GDD(OLogen) and TE(Ologen) were the most effective interventions in terms of surgical success rate and IOPR at 12 months postoperatively, respectively. However, considering the limitations of this network meta-analysis, more well-designed and high-quality trials are needed to include additional interventions beyond those currently discussed. More randomized controlled trials are also needed to strengthen the current conclusions.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eCook C, Foster P (2012) Epidemiology of glaucoma: what's new? 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Eye 2007/01/01 21(1):65\u0026ndash;70. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1038/sj.eye.6702125\u003c/span\u003e\u003cspan address=\"10.1038/sj.eye.6702125\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003eTable 1 The acronyms of the included interventions\u003c/p\u003e\n\u003cdiv\u003e\n \u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"643\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 44.79%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAcronym\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 55.21%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eInterventions\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 44.79%;\"\u003e\n \u003cp\u003eTE\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 55.21%;\"\u003e\n \u003cp\u003eTrabeculectomy\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 44.79%;\"\u003e\n \u003cp\u003eTE(AM)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 55.21%;\"\u003e\n \u003cp\u003eTE with antimetabolites\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 44.79%;\"\u003e\n \u003cp\u003eGDD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 55.21%;\"\u003e\n \u003cp\u003eGlaucoma drainage device\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 44.79%;\"\u003e\n \u003cp\u003eGDD(Ologen)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 55.21%;\"\u003e\n \u003cp\u003eGDD with ologen\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 44.79%;\"\u003e\n \u003cp\u003eTE(AM+Ologen)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 55.21%;\"\u003e\n \u003cp\u003eTE(AM) combined with Ologen\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 44.79%;\"\u003e\n \u003cp\u003eTE(AM+antiVEGF soaked Ologen)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 55.21%;\"\u003e\n \u003cp\u003eTE(AM) combined with anti-vascular endothelial growth factor (antiVEGF) socked\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 44.79%;\"\u003e\n \u003cp\u003eTE(Ologen)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 55.21%;\"\u003e\n \u003cp\u003eTE combined with ologen\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 44.79%;\"\u003e\n \u003cp\u003ePhacoTE(AM)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 55.21%;\"\u003e\n \u003cp\u003ephacoemulsification combined with\u0026nbsp;TE(AM)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 44.79%;\"\u003e\n \u003cp\u003ePhacoTE(Ologen)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 55.21%;\"\u003e\n \u003cp\u003ephacoemulsification combined with\u0026nbsp;TE(Ologen)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 44.79%;\"\u003e\n \u003cp\u003eGDD(AM)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 55.21%;\"\u003e\n \u003cp\u003eGDD with antimetabolites\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 44.79%;\"\u003e\n \u003cp\u003ePhacoGDD(AM)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 55.21%;\"\u003e\n \u003cp\u003ePhacoemulsification combined with\u0026nbsp;GDD(AM)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 44.79%;\"\u003e\n \u003cp\u003eGDD(AM+Ologen)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 55.21%;\"\u003e\n \u003cp\u003eGDD(AM) combined with Ologen\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 44.79%;\"\u003e\n \u003cp\u003ePhacoGDD(AM+Ologen)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 55.21%;\"\u003e\n \u003cp\u003ephacoemulsification combined with\u0026nbsp;GDD(AM+Ologen)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 44.79%;\"\u003e\n \u003cp\u003eTE(VTS)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 55.21%;\"\u003e\n \u003cp\u003eTE with viscotrabeculo tomysynechiolysis\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 44.79%;\"\u003e\n \u003cp\u003eTE(C3F8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 55.21%;\"\u003e\n \u003cp\u003eTE with perfluoropropane\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 44.79%;\"\u003e\n \u003cp\u003eTE(GDD+AM)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 55.21%;\"\u003e\n \u003cp\u003eTE(AM) combined with GDD\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 44.79%;\"\u003e\n \u003cp\u003eTE(GDD+Ologen)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 55.21%;\"\u003e\n \u003cp\u003eTE(Ologen) combined with GDD\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n\u003cp\u003e\u003cb\u003eTable 2 is available in the Supplementary Files section.\u003c/b\u003e\u003c/p\u003e\n\u003cp\u003eTable 3 The results of surface under the cumulative ranking curve (SUCRA)\u003c/p\u003e\n\u003cdiv\u003e\n \u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"100%\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 49px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eTreatment\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 17px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eSUCRA\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 15px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ePrBest\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 18px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eMeanRank\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"4\" style=\"width: 100px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eIOPR (12 mouth)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 49px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eTE(Ologen)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 17px;\"\u003e\n \u003cp\u003e64\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 15px;\"\u003e\n \u003cp\u003e5.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 18px;\"\u003e\n \u003cp\u003e4.2\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 49px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eTE(AM)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 17px;\"\u003e\n \u003cp\u003e62.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 15px;\"\u003e\n \u003cp\u003e4.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 18px;\"\u003e\n \u003cp\u003e4.4\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 49px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eTE(C3F8)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 17px;\"\u003e\n \u003cp\u003e59\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 15px;\"\u003e\n \u003cp\u003e12.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 18px;\"\u003e\n \u003cp\u003e4.7\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 49px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eTE(VTS)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 17px;\"\u003e\n \u003cp\u003e54.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 15px;\"\u003e\n \u003cp\u003e9.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 18px;\"\u003e\n \u003cp\u003e5.1\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 49px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eGDD(AM+Ologen)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 17px;\"\u003e\n \u003cp\u003e53.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 15px;\"\u003e\n \u003cp\u003e30\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 18px;\"\u003e\n \u003cp\u003e5.2\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 49px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eTE(AM+Ologen)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 17px;\"\u003e\n \u003cp\u003e50.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 15px;\"\u003e\n \u003cp\u003e7.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 18px;\"\u003e\n \u003cp\u003e5.5\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 49px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eTE(AM+antiVEGF soaked Ologen)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 17px;\"\u003e\n \u003cp\u003e50.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 15px;\"\u003e\n \u003cp\u003e14.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 18px;\"\u003e\n \u003cp\u003e5.5\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 49px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eGDD(Ologen)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 17px;\"\u003e\n \u003cp\u003e36.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 15px;\"\u003e\n \u003cp\u003e7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 18px;\"\u003e\n \u003cp\u003e6.7\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 49px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eGDD\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 17px;\"\u003e\n \u003cp\u003e36.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 15px;\"\u003e\n \u003cp\u003e9.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 18px;\"\u003e\n \u003cp\u003e6.7\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 49px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eGDD(AM)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 17px;\"\u003e\n \u003cp\u003e33.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 15px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 18px;\"\u003e\n \u003cp\u003e7\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"4\" style=\"width: 100px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eSuccess rate\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 281px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eGDD(Ologen)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 97px;\"\u003e\n \u003cp\u003e78.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 87px;\"\u003e\n \u003cp\u003e21.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 102px;\"\u003e\n \u003cp\u003e4.4\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 281px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ePhacoTE(AM)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 97px;\"\u003e\n \u003cp\u003e74.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 87px;\"\u003e\n \u003cp\u003e8.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 102px;\"\u003e\n \u003cp\u003e5.1\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 281px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eGDD\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 97px;\"\u003e\n \u003cp\u003e70.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 87px;\"\u003e\n \u003cp\u003e3.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 102px;\"\u003e\n \u003cp\u003e5.8\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 281px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ePhacoTE(Ologen)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 97px;\"\u003e\n \u003cp\u003e62.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 87px;\"\u003e\n \u003cp\u003e8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 102px;\"\u003e\n \u003cp\u003e7.1\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 281px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ePhacoGDD(AM+Ologen)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 97px;\"\u003e\n \u003cp\u003e60.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 87px;\"\u003e\n \u003cp\u003e9.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 102px;\"\u003e\n \u003cp\u003e7.4\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 281px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eTE(Ologen+GDD)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 97px;\"\u003e\n \u003cp\u003e60.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 87px;\"\u003e\n \u003cp\u003e22.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 102px;\"\u003e\n \u003cp\u003e7.4\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 281px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eTE(VTS)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 97px;\"\u003e\n \u003cp\u003e57.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 87px;\"\u003e\n \u003cp\u003e10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 102px;\"\u003e\n \u003cp\u003e7.8\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 281px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eGDD(AM+Ologen)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 97px;\"\u003e\n \u003cp\u003e55.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 87px;\"\u003e\n \u003cp\u003e2.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 102px;\"\u003e\n \u003cp\u003e8.1\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 281px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eTE(Ologen)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 97px;\"\u003e\n \u003cp\u003e46.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 87px;\"\u003e\n \u003cp\u003e0.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 102px;\"\u003e\n \u003cp\u003e9.6\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 281px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eTE(AM)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 97px;\"\u003e\n \u003cp\u003e42.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 87px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 102px;\"\u003e\n \u003cp\u003e10.2\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 281px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eGDD(AM)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 97px;\"\u003e\n \u003cp\u003e40.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 87px;\"\u003e\n \u003cp\u003e0.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 102px;\"\u003e\n \u003cp\u003e10.5\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 281px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eTE(AM+GDD)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 97px;\"\u003e\n \u003cp\u003e39.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 87px;\"\u003e\n \u003cp\u003e1.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 102px;\"\u003e\n \u003cp\u003e10.7\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 281px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ePhacoGDD(AM)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 97px;\"\u003e\n \u003cp\u003e37\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 87px;\"\u003e\n \u003cp\u003e2.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 102px;\"\u003e\n \u003cp\u003e11.1\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 281px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eTE(AM+Ologen)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 97px;\"\u003e\n \u003cp\u003e36\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 87px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 102px;\"\u003e\n \u003cp\u003e11.2\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 281px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eTE(C3F8)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 97px;\"\u003e\n \u003cp\u003e35\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 87px;\"\u003e\n \u003cp\u003e3.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 102px;\"\u003e\n \u003cp\u003e11.4\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 281px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eTE(AM+antiVEGF soaked Ologen)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 97px;\"\u003e\n \u003cp\u003e28\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 87px;\"\u003e\n \u003cp\u003e0.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 102px;\"\u003e\n \u003cp\u003e12.5\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 281px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eTE\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 97px;\"\u003e\n \u003cp\u003e25.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 87px;\"\u003e\n \u003cp\u003e5.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 102px;\"\u003e\n \u003cp\u003e12.9\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003e*Note: IOPR, intraocular pressure reduction; SUCRA, surface under the cumulative ranking curve. (TE, trabeculectomy; TE(Ologen), TE combined with ologen; TE(AM), TE combined with antimetabolites; GDD, drainage valve implantation; GDD(AM), GDD with antimetabolites; GDD(Ologen), GDD with ologen; GDD(AM+Ologen), GDD(AM) combined with Ologen; TE(AM+Ologen), TE(AM) combined with Ologen; antiVEGF, anti-vascular endothelial growth factor; TE(AM+antiVEGF soaked Ologen), TE(AM) combined with antiVEGF socked Ologen; TE(VTS), TE with viscotrabeculo tomysynechiolysis; TE(C3F8), TE with perfluoropropane; PhacoTE(AM), phacoemulsification combined with TE and AM; PhacoTE(Ologen), phacoemulsification combined with TE and Ologen; PhacoGDD(AM), phacoemulsification combined with GDD and AM; PhacoGDD(AM+Ologen), phacoemulsification combined with GDD, Ologen and antimetabolites; TE(Ologen+GDD), TE(Ologen) combined with GDD).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 4 Loop-specific approach\u003c/strong\u003e\u003c/p\u003e\n\u003cdiv\u003e\n \u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"688\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 98px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eLoop\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 98px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eIF\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eseIF\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 66px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ez value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 85px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ep value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e95% CI\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 149px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eLoop Heterog tau2\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"7\" style=\"width: 688px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eIOPR (12 mouth)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 98px;\"\u003e\n \u003cp\u003eB-E-F\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 98px;\"\u003e\n \u003cp\u003e2.133 \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003e11.491\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 66px;\"\u003e\n \u003cp\u003e0.186\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 85px;\"\u003e\n \u003cp\u003e0.853\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113px;\"\u003e\n \u003cp\u003e(0.00, 24.65)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 149px;\"\u003e\n \u003cp\u003e0.000\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"7\" style=\"width: 688px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eSuccess rate\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 98px;\"\u003e\n \u003cp\u003eB-E-F\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 98px;\"\u003e\n \u003cp\u003e0.124\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003e0.750\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 66px;\"\u003e\n \u003cp\u003e0.166\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 85px;\"\u003e\n \u003cp\u003e0.868\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113px;\"\u003e\n \u003cp\u003e(0.00, 1.59)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 149px;\"\u003e\n \u003cp\u003e0.000\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 98px;\"\u003e\n \u003cp\u003eJ-L-M\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 98px;\"\u003e\n \u003cp\u003e0.396\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003e0.959\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 66px;\"\u003e\n \u003cp\u003e0.413\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 85px;\"\u003e\n \u003cp\u003e0.680\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113px;\"\u003e\n \u003cp\u003e(0.00, 2.28)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 149px;\"\u003e\n \u003cp\u003e0.000\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 98px;\"\u003e\n \u003cp\u003eJ-K-M\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 98px;\"\u003e\n \u003cp\u003e0.396\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003e1.083\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 66px;\"\u003e\n \u003cp\u003e0.365\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 85px;\"\u003e\n \u003cp\u003e0.715\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113px;\"\u003e\n \u003cp\u003e(0.00, 2.52)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 149px;\"\u003e\n \u003cp\u003e0.000\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"7\" valign=\"top\" style=\"width: 688px;\"\u003e\n \u003cp\u003eLoop-specific approach is aimed to examine the inconsistency of closed loop. The closer IF is to 0, the better of the direct and indirect evideces\u0026apos; consistency.\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003eNote: A=TE(Ologen), B=TE(AM), C=GDD(Ologen), D=GDD, E=TE(AM+Ologen), F=TE(AM+antiVEGF soaked Ologen), G=TE, H=PhacoTE(AM), I=PhacoTE(Ologen), J= GDD(AM+Ologen), K=PhacoGDD(AM), L=PhacoGDD(AM+Ologen), M=GDD(AM), N=TE(VTS), O=TE(C3F8), P=TE(AM+GDD), Q=TE(Ologen+GDD)\u003c/p\u003e\n\u003cp\u003e\u003cb\u003eTable 5 is available in the Supplementary Files section.\u003c/b\u003e\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"","lastPublishedDoi":"10.21203/rs.3.rs-5813928/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-5813928/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eImportance\u003c/h2\u003e \u003cp\u003eThis network meta-analysis was aimed to evaluate how Ologen will do when combined with different interventions for glaucoma patients.\u003c/p\u003e\u003ch2\u003eObjective\u003c/h2\u003e \u003cp\u003eTo compare the effectiveness and safety of surgical treatments combined with Ologen and other commonly used treatments for glaucoma.\u003c/p\u003e\u003ch2\u003eData Sources and Study Selection\u003c/h2\u003e \u003cp\u003eThis network meta-analysis included randomized or non-randomized controlled trials and retrospective trials that compared interventions concerning Ologen and other treatments for glaucoma. The following databases were searched up to January 1, 2023: PubMed, Embase, Cochrane Library and Web of Science.\u003c/p\u003e\u003ch2\u003eData Extraction and Synthesis\u003c/h2\u003e \u003cp\u003e Data extraction, quality and validity assessing were under the guidelines of 'Preferred Reporting Items for Systematic Reviews and Meta-Analyses'. The demographic character of the included patients and outcomes was extracted independently by 2 investigators. Random-effects model was used to pool the estimate values.\u003c/p\u003e\u003ch2\u003eMean outcomes and measures\u003c/h2\u003e \u003cp\u003eMean differences for intraocular pressure reduction at 12 months postoperatively and the odds ratios for success rate at the end of follow-up time were the primary and secondary outcome. Measurement of outcomes were reported by 95% credibility intervals, and P\u0026thinsp;\u0026lt;\u0026thinsp;0.05 was considered statistically significantly.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eThis meta-analysis included 35 covering 2477 patients. We discussed 17 interventions, of which 10 had relevant outcomes in intraocular pressure reduction and 17 had relevant outcomes in success rate. When the intraocular pressure reduction was discussed, no pairwise comparison was statistically significant. While for success rate, pairwise comparisons that had statistically significant were detailed in the results and appendix section of this text. The best interventions are as follows: glaucoma drainage device combined with Ologen (success rate, surface under the cumulative ranking\u0026thinsp;=\u0026thinsp;78.9) and trabeculectomy combined with Ologen (intraocular pressure reduction 12 mouths after surgery, surface under the cumulative ranking\u0026thinsp;=\u0026thinsp;64). Adverse events were also calculated in details.\u003c/p\u003e\u003ch2\u003eConclusion and Relevance\u003c/h2\u003e \u003cp\u003eGlaucoma drainage device combined with Ologen and trabeculectomy combined with Ologen are the most effective interventions for success rate and intraocular pressure reduction at 12 months postoperatively. However, more clinical studies are still in need to confirm this conclusion and to assess the long-term safety of these interventions.\u003c/p\u003e\u003ch2\u003eTrial Registration\u003c/h2\u003e \u003cp\u003ePROSPERO Identifier: CRD42023395804\u003c/p\u003e","manuscriptTitle":"Short-term Efficacy and Safety of Ologen Collagen Matrix Implantation for Glaucoma Surgery: A Systematic Review and Network Meta-analysis","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-01-15 12:06:10","doi":"10.21203/rs.3.rs-5813928/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"efc8b09c-d1b8-40e1-9133-ce2eba9e4302","owner":[],"postedDate":"January 15th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":42740477,"name":"Ophthalmology"}],"tags":[],"updatedAt":"2025-01-15T12:06:10+00:00","versionOfRecord":[],"versionCreatedAt":"2025-01-15 12:06:10","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-5813928","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-5813928","identity":"rs-5813928","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}