Early Postoperative Bevacizumab for Preventing Neovascular Glaucoma in Phacovitrectomy for Proliferative Diabetic Retinopathy

Early Postoperative Bevacizumab for Preventing Neovascular Glaucoma in Phacovitrectomy for Proliferative Diabetic Retinopathy | 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 Article Early Postoperative Bevacizumab for Preventing Neovascular Glaucoma in Phacovitrectomy for Proliferative Diabetic Retinopathy Sunjin Hwang, Eun Hee Hong, Min Ho Kang, Yong Un Shin This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-5214895/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 07 Jan, 2025 Read the published version in Scientific Reports → Version 1 posted 12 You are reading this latest preprint version Abstract Purpose To evaluate the effectiveness of postoperative intravitreal bevacizumab (IVB) in preventing neovascular glaucoma (NVG) and identify associated risk factors in patients with proliferative diabetic retinopathy (PDR) undergoing phacovitrectomy. Methods Patients with PDR who underwent phacovitrectomy were enrolled and categorized into two subgroups based on their postoperative treatment regimen: one group received IVB within 2 months following phacovitrectomy (Group 1); the other did not receive IVB during this period (Group 2). A comparative analysis evaluated the distinguishing characteristics of the two groups after 1:1 propensity score matching. Kaplan–Meier survival analysis was utilized to determine the incidence of NVG after phacovitrectomy. Multivariate analysis with the Cox proportional hazards model identified risk factors associated with NVG postphacovitrectomy. Results A total of 220 eyes of 220 patients were investigated in this study. NVG developed in 29 eyes (13.18%). The probabilities of NVG occurrence at 6, 12, and 24 months following phacovitrectomy were 2.72%, 5.45%, and 13.18%, respectively. When comparing Groups 1 (n = 58) and 2 (n = 58), a significant difference was observed in the occurrence of NVG ( P < 0.001). In Group 1, only two cases of NVG (3.44%) were noted, whereas all other NVG cases occurred in Group 2 (16.67%). Male sex and high preoperative intraocular pressure (IOP) were associated with NVG occurrence following phacovitrectomy, and the administration of IVB within 2 months postphacovitrectomy demonstrated efficacy in preventing the development of NVG. Conclusion Male sex and high preoperative IOP were associated with a higher incidence of NVG, and postoperative IVB had a protective effect against NVG occurrence. Health sciences/Medical research/Outcomes research Health sciences/Risk factors Phacovitrectomy Neovascular glaucoma Prevention Bevacizumab Figures Figure 1 Figure 2 Introduction Proliferative diabetic retinopathy (PDR) is one of the major causes of vision loss and blindness in the working-age population worldwide. 1 It is defined as the proliferation of fragile blood vessels on the retina and the posterior surface of the vitreous, often leading to vitreous hemorrhage (VH), a condition in which these fragile vessels bleed into the vitreous. This hemorrhage can obscure vision and, if left untreated, may result in permanent vision loss. The incidence of cataract development is notably higher in patients with diabetes, being threefold more prevalent compared to nondiabetic individuals. 2 This increased propensity often results in the concurrent manifestation of VH and cataracts within this patient demographic. Additionally, the occurrence of cataract formation postvitrectomy has significantly increased. 3 Consequently, the integration of phacovitrectomy as a surgical strategy offers a comprehensive and effective treatment approach for these patients, simultaneously addressing both cataract and vitreoretinal pathologies. The merits of combined surgical procedures are manifold, including enhanced intraoperative visualization and the obviation of subsequent cataract surgery, as documented in recent studies. 4 Additionally, there is a compelling rationale for opting for combined surgery, given that subsequent cataract operations in vitrectomized eyes can be fraught with complexities, such as an excessively deep anterior chamber and zonular dehiscence. 4 However, acknowledging the drawbacks of combined surgery, which include its inherently complex nature and extended duration that may elevate the risk of both intraoperative and postoperative complications, is important. 5 According to a recent meta-analysis 6 , neovascular glaucoma (NVG) occurs more frequently in cases of phacovitrectomy than in those of vitrectomy alone. Postvitrectomy aphakia acts as a risk factor for NVG development. Removal of the lens may eliminate the protective barrier, allowing various angiogenic factors to move from the back to the front, which could lead to its occurrence. Despite advancements in vitrectomy techniques for treating advanced PDR, the prevalence of NVG remains significant, with an incidence rate ranging 2–12%. 7-9 Furthermore, growing evidence suggests a correlation between intraocular levels of vascular endothelial growth factor (VEGF) and NVG development. 10 Consequently, the impact of postoperative intravitreal bevacizumab (IVB) on NVG presents an important and emerging area of inquiry in the field. We aimed to investigate the risk factors associated with NVG development of NVG following phacovitrectomy in patients with PDR. Additionally, we sought to determine the efficacy of IVB injections for the postoperative prevention of NVG. Results A total of 220 eyes were analyzed. Among them, NVG occurred in 29 eyes (13.18%). The probabilities of NVG occurrence at 6 and 12 months after phacovitrectomy were 4.54% and 10.45%, respectively. The average time to NVG manifestation was 9.53 ± 4.50 months. The mean follow-up period was 49.69 ± 22.29 months. Table 1 compares the baseline characteristics of Groups 1 (n = 58) and 2 (n = 162). Following the matching of age and sex through propensity scores, both groups ultimately included 58 patients each. Group 1 had a significantly lower incidence of NVG (3.44% vs. 16.67%, P 0.05). Most patients with NVG experience NVG onset within 1 year, with approximately 35% developing NVG within 6 months. Table 1 Baseline demographic and clinical data of all patients Unmatched cohort Matched cohort Group 1 (n = 58) Group 2 (n = 162) P -value SMD Group 1 (n = 58) Group 2 (n = 58) P -value SMD Age (years) 55.10 ± 8.75 56.68 ± 8.53 0.230* 0.169 55.10 ± 8.75 55.04 ± 8.11 0.887* 0.025 Sex (male) 36 105 0.751† 0.330 36 35 0.851† 0.066 Laterality (Right) 32 76 0.289† 0.178 32 29 0.377† 0.187 Baseline IOP (mmHg) 15.96 ± 3.37 15.69 ± 3.38 0.605* 0.036 15.96 ± 3.37 15.98 ± 3.70 0.883* 0.026 Duration of DM (years) 11.43 ± 8.86 11.78 ± 8.42 0.791* 0.004 11.43 ± 8.86 11.53 ± 8.51 0.927* 0.016 HbA1c (%) 7.46 ± 1.32 7.78 ± 1.80 0.214* 0.178 7.46 ± 1.32 7.77 ± 1.73 0.338* 0.170 Cr (mg/dL) 1.94 ± 2.54 1.60 ± 1.93 0.295* 0.150 1.94 ± 2.54 1.59 ± 1.91 0.422* 0.143 Preoperative PRP 41 102 0.337† 0.124 41 45 0.848† 0.034 Ischemic stroke (cardiac or cerebral) 3 10 0.782‡ 0.060 3 1 0.128‡ 0.162 Systemic hypertension 32 88 0.911† 0.052 32 31 0.479† 0.156 Intraoperative tamponade 9 32 0.477† 0.156 9 16 0.180† 0.276 Follow up period (months) 48.5 ± 19.47 50.97 ± 21.86 0.129* 0.125 48.5 ± 19.47 49.92 ± 20.79 0.324† 0.097 Incidence of NVG 2 27 < 0.001† 0.338 2 21 < 0.001† 0.766 *Mann–Whitney U test. †Chi-square test. ‡Fisher’s exact test Cr, creatinine; DM, diabetes mellitus; HbA1c, hemoglobin A1c; IOP, intraocular pressure; NVG, neovascular glaucoma; PRP, pan-retinal photocoagulation; SMD, standardized mean difference. Group1 was defined as individuals who received IVB within 2 months after the phacovitrectomy. Group 2 included patients who did not receive IVB within 2 months of phacovitrectomy. Group 1 was defined as individuals who received IVB within 2 months after the phacovitrectomy. Group 2 included patients who did not receive IVB within 2 months of phacovitrectomy. The Cox proportional hazards model identified that male sex (HR = 4.526 [1.560–13.132], P = 0.005) and high preoperative IOP (HR = 1.115 [1.024–1.214], P = 0.012) increased the incidence of NVG, and that receiving IVB within 2 months postsurgery had a protective effect against the development of NVG (HR = 0.194 [0.046–0.815], P = 0.025) (Table 2 ). Table 2 Likelihood of postoperative NVG Univariate analysis Multivariate analysis Variables HR 95% CI P -value HR 95% CI P -value Age (years) 0.996 0.946–1.049 0.891 Sex (male) 4.740 1.627–13.815 0.004 4.526 1.560–13.132 0.005 Laterality (Right) 1.517 0.692–3.323 0.298 Baseline IOP (mmHg) 1.113 1.018–1.218 0.019 1.115 1.024–1.214 0.012 Duration of DM (years) 1.007 0.952–1.064 0.817 HbA1c (%) 0.997 0.768–1.294 0.981 Cr (mg/dL) 0.682 0.440–1.058 0.087 Preoperative PRP 1.816 0.749–4.404 0.187 Ischemic stroke (cardiac or cerebral) 1.121 0.141–8.897 0.914 Systemic hypertension 0.728 0.329–1.613 0.434 Intraoperative tamponade 0.633 0.230–1.742 0.376 Follow up period (months) Postoperative IVB (within 2 months) 0.179 0.042–0.760 0.020 0.194 0.046–0.815 0.025 Cr, creatinine; CI, confidence interval; DM, diabetes mellitus; HbA1c, hemoglobin A1c; HR, hazard ratio; IOP, intraocular pressure; IVB, intravitreal bevacizumab; NVG, neovascular glaucoma; PRP, pan-retinal photocoagulation. In this study, no ocular or systemic side effects related to IVB, including systemic thromboembolic events or endophthalmitis, were observed. A total of 25 eyes (11.36%) experienced postoperative vitreous hemorrhage. Of these, 15 required vitrectomy. Tractional retinal detachment occurred in 19 eyes (8.63%) for which silicone oil tamponade was performed. Overall, 29 eyes (13.18%) developed NVG; in all these cases, IOP was controlled with maximum tolerated medical therapy. Glaucoma surgery was performed when intraocular pressure could not be controlled despite maximum tolerated medical therapy. Ahmed valve implantation was performed in seven eyes, and trabeculectomy was performed in another seven eyes. Intraocular pressure returned to normal in all cases after surgery. When comparing the number of IVB injections within 2 years after phacovitrectomy, the average was 1.27 ± 1.77 injections in the group without NVG, and 3.17 ± 2.95 injections in the group with NVG ( P = 0.002). The final BCVA was lower in the group with NVG compared to the group without NVG (0.05 ± 1.95 vs 0.27 ± 0.04, P < 0.001). Discussion We aimed to report the risk factors for NVG during phacovitrectomy and the utility of early postoperative IVB. The prevalence of NVG in this study was 13.18%, which is higher than that reported in recent studies. 7 – 9 However, this incidence rate can vary depending on the surgical method, patient characteristics, and observation period. Our study involved a lengthy follow-up period of 49.69 ± 22.29 months, and phacovitrectomy was performed on all patients. Although it is a somewhat older study, the incidence of NVG after vitrectomy in nonphakic eyes has been reported to be between 20% and 39%. 11–13 Our team observed a higher incidence of NVG in patients undergoing phacovitectomy, and we confirmed that the group receiving IVB after surgery had a lower occurrence of postoperative NVG (16.67 vs 3.44%, P < 0.001). Previous studies conducted before the 1980s reported NVG incidence rates ranging 10–23%, which decreased to 2–15% after 1980s owing to advancements in equipment, enhanced surgical expertise, preoperative PRP, and the shift from pars plana lensectomy to phacoemulsification. 11 Aphakia was identified as the primary risk factor for NVG postvitrectomy in earlier studies, predominantly using the 20-gauge system and conventional surgical techniques while excluding patients who underwent lensectomy for aphakia. A meta-analysis of 5,161 patients from 26 studies conducted between 1993 and 2020 revealed a varied NVG incidence ranging 0.3–23.6%; however, 14 the choice of gauge during surgery and the use of antiVEGF did not significantly impact NVG incidence; however, elevated preoperative IOP, combined preoperative or intraoperative cataract surgery, and postoperative VH were linked to a higher NVG incidence. In a previously conducted but unpublished study by our group comparing the vitrectomy-only group to the combined phacovitrectomy group in patients with PDR, the risk of NVG was higher in the phacovitectomy group (12.71%) than in the vitrectomy-only group (3.9%) ( P = 0.001). Phacovitrectomy is increasingly performed nowadays because of its advantages, such as improving visibility during surgery 4 and addressing the issue of cataract worsening after vitrectomy in a single procedure. 3 However, noting the potential side effects of this surgery is always important. VEGF triggers the neovascularization of the iris, angle, and connective tissue membrane, leading to the subsequent formation of synechiae in the peripheral iris and trabecular meshwork. 15 In eyes that are both vitrectomized and lensectomized, the transport of oxygen, various growth factors, and cytokines through the vitreous cavity is accelerated. 16 Oxygen moves via diffusion and convection from the anterior chamber, where the partial pressure of oxygen is typically higher than at the retina, to the posterior segment of the eye. This oxygen movement results in hypoxia in the anterior segment and iris. Concurrently, growth factors, such as VEGF, are more efficiently transported from the retina to the iris. The combination of hypoxia in the anterior segment and the influx of additional VEGF from the retina promotes neovascularization of the iris, causing NVG. Conversely, in cases where only a vitrectomy is performed while preserving the lens, oxygen saturation within the retina tends to stabilize. 17 The surgery removes all neovascular and fibrovascular tissues, and the removal of the vitreous can aid in perfusing the remaining ischemic retina. Additionally, the vitreous is washed away; therefore, the concentration of VEGF within the vitreous significantly decreases compared to presurgery levels. 18 Therefore, a relatively lower likelihood of developing NVG is anticipated in these circumstances. Cataract surgery is known to trigger inflammation after the procedure, and studies have indicated that individuals diagnosed with NVG exhibit increased levels of inflammatory cytokines within the anterior chamber of the eye. 19 Moreover, studies have suggested that NVG is more prevalent in individuals with uveitis, implying that inflammation alone could increase the likelihood of NVG. 20 Another condition that can arise due to inflammation following the removal of the crystalline lens is pseudophakic cystoid macular edema (PCME), also known as Irvine–Gass syndrome. This condition typically occurs 4–6 weeks after surgery, with most cases developing within 3 months. 21 Topical NSAIDs can be used to prevent PCME. Recent studies have indicated that the incidence of PCME is higher in cases where combined phacovitrectomy is performed compared to vitrectomy alone in pseudophakic eyes. 22 This finding aligns with the results of this study, which shows a higher incidence of NVG following phacovitrectomy in patients with PDR. Furthermore, considering that the timing of PCME and NVG onset is similar, the early administration of postoperative bevacizumab could be further supported as a rationale for prevention. Administering bevacizumab, an anti-VEGF antibody, through intravitreal injection in patients with PDR, has been observed to quickly cause the regression of neovascularization in both the retina and iris. 23 Furthermore, reports suggest that administering bevacizumab before vitrectomy in cases of PDR can reduce intraoperative bleeding and facilitate surgery, 24 and that administering bevacizumab during surgery can lead to a reduction in VH after surgery. 25 However, no studies have demonstrated the effectiveness of preoperative or intraoperative bevacizumab in relation to postoperative NVG. In a study on the pharmacokinetics of IVB, bevacizumab administered via the intravitreal route could also be detected in the anterior chamber. 26 This suggests that administering bevacizumab intravitreally may contribute to lowering the concentration of VEGF in the anterior chamber, which could reduce the incidence of NVG. Two studies have discussed the relationship between postoperative anti-VEGF use and the incidence of NVG. Kwon et al. 27 reported that the use of bevacizumab after phacovitrectomy and vitrectomy (102 of 127 patients who underwent phacovitrectomy) increased the incidence of NVG. However, in their study, bevacizumab was only administered in cases of postoperative VH, making it challenging to determine whether the increase in NVG was due to postoperative VH or the injection of bevacizumab itself. Another study 28 suggested that postoperative administration of ranibizumab reduced the incidence of NVG. However, in this study, only 43.32% of cases involved phacovitrectomy. In our study, we observed a decrease in the incidence of NVG after phacovitrectomy when bevacizumab was administered within 2 months. Considering that the average onset time of NVG was 9.53 ± 4.50 months, with the earliest case occurring at 2.5 months, we determined that administering bevacizumab within 2 months could be effective in preventing NVG. Male sex and a high preoperative IOP increased the incidence of NVG. Several studies examining the incidence of NVG have reported a higher prevalence in males 29 . Studies have shown that the incidence of stroke is also higher in men than in women 30 ; hence, it can be presumed that there is a clear sex predilection affecting the incidence of ischemia. Studies have confirmed the association between high preoperative IOP and a higher incidence of NVG. In our study, we also found that a high IOP before surgery increased the incidence of NVG 29 . Although neovascularization of the iris and angle was not detected in the preoperative examination, subtle NVG that was difficult to detect may have been present prior to surgery. The limitations of our study include its retrospective design. We were unable to measure or compare the actual concentrations of VEGF in the anterior chamber. Additionally, we were unable to directly measure and compare nonperfusion areas postoperatively. In future prospective studies, our research team intends to quantitatively measure preoperative and postoperative VEGF and cytokine levels as well as the nonperfusion area to demonstrate that NVG occurs more frequently after phacovitrectomy and that postoperative bevacizumab is useful in preventing NVG. In conclusion, our study revealed that male sex and a high preoperative IOP were associated with a higher incidence of NVG in patients with PDR undergoing phacovitrectomy. Additionally, administering IVB within 2 months of surgery can reduce the occurrence of NVG, and this approach is clinically beneficial. Materials and Methods Study design This retrospective observational case-control study enrolled patients with PDR who had phacovitrectomy for VH at a single tertiary medical center (Hanyang University Guri Hospital in South Korea) between January 2016 and January 2022. This retrospective study was approved by the Institutional Review Board of Hanyang University Guri Hospital (2023-12-023). All the procedures were performed in strict compliance with the ethical standards of the Declaration of Helsinki. The informed consent was waived by the Institutional Review Board of Hanyang University Guri Hospital because of the retrospective nature of the study. Patient population We collected data on all patients who underwent phacovitrectomy from the medical information team between 2016 and 2022 in a consecutive manner. At the request of the medical information team, we gathered a consecutive series of patients with diagnoses code including “PDR,” “tractional retinal detachment (tRD),” or “VH,” along with those who had a charge for “vitrectomy,” and “phacoemulsification.” The patient cohort comprised of individuals who underwent vitrectomy for conditions such as VH, tRD, and epiretinal membrane. We reviewed the medical records, and the exclusion criteria were as follows: eyes treated with vitrectomy due to any retinal diseases, received vitrectomy-only procedure, intraocular injection of triamcinolone acetonide, eyes with severe intraocular inflammation, a history of glaucoma or preoperative rubeosis, and lost to follow-up before the period of 2 years (Fig. 2 ). Each patient's medical records encompassed comprehensive general and ocular histories and were thoroughly documented. These included detailed slit-lamp examinations, intraocular pressure (IOP) measurements, assessment of the best-corrected visual acuity (BCVA), evaluation of the presence or absence of preoperative panretinal photocoagulation (PRP), and identification of underlying systemic hypertension. Additionally, a history of cardiac or cerebral ischemic stroke was noted, along with the application of intraoperative tamponade. The follow-up period for all patients was extended beyond 1 year. Preoperative IVB was administered to all patients within 1 week prior to surgery. Postoperative NVG was characterized by the presence of the anterior segment (the iris or angle) neovascularization, as identified through slit-lamp and gonioscopic examinations following vitrectomy. Additionally, a postoperative IOP exceeding 22 mmHg, confirmed during a subsequent visit, was also a defining criterion for NVG. All patients were followed up for a minimum of 2 years and the mean follow-up period was 49.69 ± 22.29 months. Surgical techniques Surgery was performed by an experienced retinal surgeon (Y.U.S.) using a Constellation Vision System (Alcon Laboratories, Inc., Fort Worth, TX, USA) with wide-angle viewing using 23- or 25-gauge instruments. In each surgical case, phacoemulsification was performed before the vitreoretinal procedure. When intraocular lens (IOL) calculations were impeded by retinal detachments or VHs, axial length measurements were obtained using A-scan ultrasound. These measurements were corroborated with the full optical biometry of the unaffected contralateral eye. Following the completion of phacoemulsification and acrylic foldable IOL implantation via the primary 2.8-mm corneal incision in the posterior chamber, all viscoelastic substances were meticulously aspirated. To prevent the collapse of the anterior chamber during vitrectomy, a 10 − 0 nylon suture was placed on the clear corneal wound as a prophylactic measure. After cataract extraction, a standard 3-port 23- or 25-gauge pars plana vitrectomy was performed. The surgical procedure was concluded with fluid-air exchange and gas or silicone oil injections in scenarios where retinal breaks or retinal detachments were detected. Additionally, endolaser treatment was applied in all patients to complete panretinal photocoagulation. Postoperatively, all patients were prescribed topical antibiotics, which were administered four times daily for a duration of 2 weeks. Topical steroids were applied 4–8 times daily, with a gradual reduction in frequency over time. Topical nonsteroidal anti-inflammatory drugs were also prescribed twice daily for a period of 2 months following surgery. Statistical analysis Data analysis was performed using the SPSS software, version 29.0 (IBM Corp., Armonk, NY, USA). The patients were divided into two groups for comparative analysis: one group received IVB within 2 months after surgery (Group 1), whereas the other group did not receive postoperative IVB within 2 months after surgery (Group 2). Initially, Group 1 consisted of 58 patients while Group 2 had 162 patients. To minimize demographic differences between the groups in this retrospective study, we conducted a propensity score matching, ensuring that age and sex distributions were balanced. We used the nearest neighbor method for matching in a 1:1 ratio. The effectiveness of this matching was assessed by calculating the absolute mean differences in the propensity scores. In the analysis of two-group comparisons, parametric variables were evaluated using Student's t-test, whereas nonparametric data were assessed using the Mann–Whitney U test. For categorical data, Pearson’s chi-square test was employed, and in instances where any cell of a contingency table contained values less than five, Fisher’s exact test was used. Kaplan–Meier survival analysis was used to ascertain the incidence of NVG following phacovitrectomy in patients with PDR. To identify risk factors and quantify their hazard ratios (HR) for the development of NVG postphacovitrectomy in patients with PDR, multivariate analysis using the Cox proportional hazards model was conducted. The analysis encompassed a range of potential risk factors, including patient sex, age, baseline IOP (defined as the average of three consecutive IOP measurements before vitrectomy), duration of diabetes, systemic hypertension, history of ischemic stroke (cardiac or cerebral), serum hemoglobin A1c levels, serum creatinine concentration, history of preoperative panretinal photocoagulation, use of gas or silicone oil tamponade during vitrectomy, and postoperative IVB within 2 months. Statistical significance was established at a P -value threshold of < 0.05 Declarations Authorship contribution Sunjin Hwang : Writing – original draft, Writing – review & editing, Methodology, Data curation, Formal analysis. Eun Hee Hong : Data curation, Formal analysis . Min Ho Kang : Data curation, Formal analysis. Yong Un Shin : Conceptualization, Methodology, Writing – review & editing, Supervision. Acknowledgments We would like to thank Editage (www.editage.co.kr) for English language editing. Funding/Support: No specific grants from public, commercial, or non-profit funding agencies supported this research.. Disclosure(s) : All authors have completed and submitted the disclosures form. There are no conflicts of interest for any author. Data Availability : The datasets used and/or analyzed in this study can be obtained from the corresponding author upon reasonable request. References Song P, Yu J, Chan KY, Theodoratou E, Rudan I. 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Cite Share Download PDF Status: Published Journal Publication published 07 Jan, 2025 Read the published version in Scientific Reports → Version 1 posted Editorial decision: Revision requested 18 Nov, 2024 Reviews received at journal 17 Nov, 2024 Reviews received at journal 25 Oct, 2024 Reviews received at journal 25 Oct, 2024 Reviewers agreed at journal 20 Oct, 2024 Reviewers agreed at journal 15 Oct, 2024 Reviewers agreed at journal 13 Oct, 2024 Reviewers invited by journal 13 Oct, 2024 Editor assigned by journal 13 Oct, 2024 Editor invited by journal 08 Oct, 2024 Submission checks completed at journal 07 Oct, 2024 First submitted to journal 06 Oct, 2024 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. 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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-5214895","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":379253760,"identity":"894ff3f4-1e8c-4c2d-9e69-59d468954e25","order_by":0,"name":"Sunjin Hwang","email":"","orcid":"","institution":"Hanyang University Guri Hospital, Hanyang University College of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Sunjin","middleName":"","lastName":"Hwang","suffix":""},{"id":379253761,"identity":"4e5e0111-38fe-4d65-90ee-84ec835a33e2","order_by":1,"name":"Eun Hee Hong","email":"","orcid":"","institution":"Hanyang University Guri Hospital, Hanyang University College of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Eun","middleName":"Hee","lastName":"Hong","suffix":""},{"id":379253762,"identity":"79e18130-04c7-4cf8-be5a-f883f3ea3d52","order_by":2,"name":"Min Ho Kang","email":"","orcid":"","institution":"Hanyang University Guri Hospital, Hanyang University College of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Min","middleName":"Ho","lastName":"Kang","suffix":""},{"id":379253763,"identity":"f4982415-8ce6-400b-8967-2a54f36db924","order_by":3,"name":"Yong Un Shin","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA5UlEQVRIiWNgGAWjYHACNoYEBpsEFAFitKSRqoWB4TAJWgxupD978HDH+Tz+2T2Gnwt+McjzN7ClfcCvJcfcIPHM7WKJO2eMpWf2MRjOOMB2eAYBLWwSiW23Extu5BhI8/YwMG5gYG8m6DCglnOJ82/kGP8GarEnQkuCGVDLgcQNN3LMpHl+MCRuYGA7jFeL5Jk3IC3JiRtvpJVZ8zZIJM84zJaMVwvf8fRnkj/b7BLn3UjefJvnj41tf3ubMV4tCgfgTA4DBsY2CQYGZrwaGBjkG+BM9gcMDH8IKB8Fo2AUjIIRCQBPpExZPL8dEQAAAABJRU5ErkJggg==","orcid":"","institution":"Hanyang University Guri Hospital, Hanyang University College of Medicine","correspondingAuthor":true,"prefix":"","firstName":"Yong","middleName":"Un","lastName":"Shin","suffix":""}],"badges":[],"createdAt":"2024-10-07 02:23:14","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-5214895/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-5214895/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1038/s41598-025-85667-y","type":"published","date":"2025-01-07T15:57:46+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":70506387,"identity":"7b9580fb-573a-4b81-a84a-96db2abaa6bb","added_by":"auto","created_at":"2024-12-03 23:38:07","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":49894,"visible":true,"origin":"","legend":"\u003cp\u003eThe cumulative probability of neovascular glaucoma (NVG) following phacovitrectomy is graphically represented for Groups 1 and 2. The horizontal axis displays the time elapsed postsurgery in months, whereas the vertical axis shows the incidence of NVG in percentages. A significant difference in the incidence rate of NVG between Group 1 and Group 2 is observed (\u003cem\u003eP\u003c/em\u003e\u0026lt;0.001).\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-5214895/v1/1f64224df7cdde2769df4ad2.png"},{"id":70506388,"identity":"bab2f4f0-8aab-4886-a5b0-0750d5f4771f","added_by":"auto","created_at":"2024-12-03 23:38:07","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":58864,"visible":true,"origin":"","legend":"\u003cp\u003eFlow chart of enrolled patients and exclusion.\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-5214895/v1/03a3513c058ef1f830380497.png"},{"id":73693974,"identity":"6fbea267-1155-45eb-880a-bdf6a1ba59e9","added_by":"auto","created_at":"2025-01-13 16:10:09","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":749264,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-5214895/v1/116a867e-56b3-4d73-acf9-94aa2e506e42.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Early Postoperative Bevacizumab for Preventing Neovascular Glaucoma in Phacovitrectomy for Proliferative Diabetic Retinopathy","fulltext":[{"header":"Introduction","content":"\u003cp\u003eProliferative diabetic retinopathy (PDR) is one of the major causes of vision loss and blindness in the working-age population worldwide.\u003csup\u003e1\u003c/sup\u003e It is defined as the proliferation of fragile \u0026nbsp;blood vessels on the retina and the posterior surface of the vitreous, often leading to vitreous hemorrhage (VH), a condition in which these fragile vessels bleed into the vitreous. This hemorrhage can obscure vision and, if left untreated, may result in permanent vision loss.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe incidence of cataract development is notably higher in patients with diabetes, being threefold more prevalent compared to nondiabetic individuals.\u003csup\u003e2\u003c/sup\u003e This increased propensity often results in the concurrent manifestation of VH and cataracts within this patient demographic. Additionally, the occurrence of cataract formation postvitrectomy has significantly increased.\u003csup\u003e3\u003c/sup\u003e Consequently, the integration of phacovitrectomy as a surgical strategy offers a comprehensive and effective treatment approach for these patients, simultaneously addressing both cataract and vitreoretinal pathologies.\u003c/p\u003e\n\u003cp\u003eThe merits of combined surgical procedures are manifold, including enhanced intraoperative visualization and the obviation of subsequent cataract surgery, as documented in recent studies.\u003csup\u003e4\u003c/sup\u003e Additionally, there is a compelling rationale for opting for combined surgery, given that subsequent cataract operations in vitrectomized eyes can be fraught with complexities, such as an excessively deep anterior chamber and zonular dehiscence.\u003csup\u003e4\u003c/sup\u003e However, acknowledging the drawbacks of combined surgery, which include its inherently complex nature and extended duration that may elevate the risk of both intraoperative and postoperative complications, is important.\u003csup\u003e5\u003c/sup\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAccording to a recent meta-analysis\u003csup\u003e6\u003c/sup\u003e, neovascular glaucoma (NVG) occurs more frequently in cases of phacovitrectomy than in those of vitrectomy alone. Postvitrectomy aphakia acts as a risk factor for NVG development. Removal of the lens may eliminate the protective barrier, allowing various angiogenic factors to move from the back to the front, which could lead to its occurrence. Despite advancements in vitrectomy techniques for treating advanced PDR, the prevalence of NVG remains significant, with an incidence rate ranging 2\u0026ndash;12%.\u003csup\u003e7-9\u003c/sup\u003e Furthermore, growing evidence suggests a correlation between intraocular levels of vascular endothelial growth factor (VEGF) and NVG development.\u003csup\u003e10\u003c/sup\u003e Consequently, the impact of postoperative intravitreal bevacizumab (IVB) on NVG presents an important and emerging area of inquiry in the field.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eWe aimed to investigate the risk factors associated with NVG development of NVG following phacovitrectomy in patients with PDR. Additionally, we sought to determine the efficacy of IVB injections for the postoperative prevention of NVG.\u0026nbsp;\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eA total of 220 eyes were analyzed. Among them, NVG occurred in 29 eyes (13.18%). The probabilities of NVG occurrence at 6 and 12 months after phacovitrectomy were 4.54% and 10.45%, respectively. The average time to NVG manifestation was 9.53\u0026thinsp;\u0026plusmn;\u0026thinsp;4.50 months. The mean follow-up period was 49.69\u0026thinsp;\u0026plusmn;\u0026thinsp;22.29 months.\u003c/p\u003e \u003cp\u003eTable\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e compares the baseline characteristics of Groups 1 (n\u0026thinsp;=\u0026thinsp;58) and 2 (n\u0026thinsp;=\u0026thinsp;162). Following the matching of age and sex through propensity scores, both groups ultimately included 58 patients each. Group 1 had a significantly lower incidence of NVG (3.44% vs. 16.67%, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001) than Group 2 (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). No significant differences were observed in other factors between the two groups (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026gt;\u0026thinsp;0.05). Most patients with NVG experience NVG onset within 1 year, with approximately 35% developing NVG within 6 months.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eBaseline demographic and clinical data of all patients\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"9\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c9\" colnum=\"9\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colspan=\"4\" nameend=\"c5\" namest=\"c2\"\u003e \u003cp\u003eUnmatched cohort\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"4\" nameend=\"c9\" namest=\"c6\"\u003e \u003cp\u003eMatched cohort\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eGroup 1 (n\u0026thinsp;=\u0026thinsp;58)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eGroup 2 (n\u0026thinsp;=\u0026thinsp;162)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cem\u003eP\u003c/em\u003e-value\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eSMD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eGroup 1 (n\u0026thinsp;=\u0026thinsp;58)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eGroup 2 (n\u0026thinsp;=\u0026thinsp;58)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e\u003cem\u003eP\u003c/em\u003e-value\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eSMD\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge (years)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e55.10\u0026thinsp;\u0026plusmn;\u0026thinsp;8.75\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e56.68\u0026thinsp;\u0026plusmn;\u0026thinsp;8.53\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.230*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.169\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e55.10\u0026thinsp;\u0026plusmn;\u0026thinsp;8.75\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e55.04\u0026thinsp;\u0026plusmn;\u0026thinsp;8.11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.887*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e0.025\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSex (male)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e36\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e105\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.751\u0026dagger;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.330\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e36\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e35\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.851\u0026dagger;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e0.066\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLaterality (Right)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e32\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e76\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.289\u0026dagger;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.178\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e32\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e29\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.377\u0026dagger;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e0.187\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBaseline IOP (mmHg)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e15.96\u0026thinsp;\u0026plusmn;\u0026thinsp;3.37\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e15.69\u0026thinsp;\u0026plusmn;\u0026thinsp;3.38\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.605*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.036\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e15.96\u0026thinsp;\u0026plusmn;\u0026thinsp;3.37\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e15.98\u0026thinsp;\u0026plusmn;\u0026thinsp;3.70\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.883*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e0.026\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDuration of DM (years)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e11.43\u0026thinsp;\u0026plusmn;\u0026thinsp;8.86\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e11.78\u0026thinsp;\u0026plusmn;\u0026thinsp;8.42\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.791*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.004\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e11.43\u0026thinsp;\u0026plusmn;\u0026thinsp;8.86\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e11.53\u0026thinsp;\u0026plusmn;\u0026thinsp;8.51\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.927*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e0.016\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHbA1c (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7.46\u0026thinsp;\u0026plusmn;\u0026thinsp;1.32\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7.78\u0026thinsp;\u0026plusmn;\u0026thinsp;1.80\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.214*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.178\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e7.46\u0026thinsp;\u0026plusmn;\u0026thinsp;1.32\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e7.77\u0026thinsp;\u0026plusmn;\u0026thinsp;1.73\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.338*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e0.170\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCr (mg/dL)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.94\u0026thinsp;\u0026plusmn;\u0026thinsp;2.54\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.60\u0026thinsp;\u0026plusmn;\u0026thinsp;1.93\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.295*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.150\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1.94\u0026thinsp;\u0026plusmn;\u0026thinsp;2.54\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e1.59\u0026thinsp;\u0026plusmn;\u0026thinsp;1.91\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.422*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e0.143\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePreoperative PRP\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e41\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e102\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.337\u0026dagger;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.124\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e41\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e45\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.848\u0026dagger;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e0.034\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIschemic stroke (cardiac or cerebral)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.782\u0026Dagger;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.060\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.128\u0026Dagger;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e0.162\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSystemic hypertension\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e32\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e88\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.911\u0026dagger;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.052\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e32\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e31\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.479\u0026dagger;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e0.156\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIntraoperative tamponade\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e32\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.477\u0026dagger;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.156\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e16\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.180\u0026dagger;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e0.276\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFollow up period (months)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e48.5\u0026thinsp;\u0026plusmn;\u0026thinsp;19.47\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e50.97\u0026thinsp;\u0026plusmn;\u0026thinsp;21.86\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.129*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.125\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e48.5\u0026thinsp;\u0026plusmn;\u0026thinsp;19.47\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e49.92\u0026thinsp;\u0026plusmn;\u0026thinsp;20.79\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.324\u0026dagger;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e0.097\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIncidence of NVG\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e27\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u0026dagger;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.338\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e21\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u0026dagger;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e0.766\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e*Mann\u0026ndash;Whitney U test.\u003c/p\u003e \u003cp\u003e\u0026dagger;Chi-square test.\u003c/p\u003e \u003cp\u003e\u0026Dagger;Fisher\u0026rsquo;s exact test\u003c/p\u003e \u003cp\u003eCr, creatinine; DM, diabetes mellitus; HbA1c, hemoglobin A1c; IOP, intraocular pressure; NVG, neovascular glaucoma; PRP, pan-retinal photocoagulation; SMD, standardized mean difference.\u003c/p\u003e \u003cp\u003eGroup1 was defined as individuals who received IVB within 2 months after the phacovitrectomy.\u003c/p\u003e \u003cp\u003eGroup 2 included patients who did not receive IVB within 2 months of phacovitrectomy.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eGroup 1 was defined as individuals who received IVB within 2 months after the phacovitrectomy.\u003c/p\u003e \u003cp\u003eGroup 2 included patients who did not receive IVB within 2 months of phacovitrectomy.\u003c/p\u003e \u003cp\u003eThe Cox proportional hazards model identified that male sex (HR\u0026thinsp;=\u0026thinsp;4.526 [1.560\u0026ndash;13.132], \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.005) and high preoperative IOP (HR\u0026thinsp;=\u0026thinsp;1.115 [1.024\u0026ndash;1.214], \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.012) increased the incidence of NVG, and that receiving IVB within 2 months postsurgery had a protective effect against the development of NVG (HR\u0026thinsp;=\u0026thinsp;0.194 [0.046\u0026ndash;0.815], \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.025) (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eLikelihood of postoperative NVG\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"8\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colspan=\"4\" nameend=\"c5\" namest=\"c2\"\u003e \u003cp\u003eUnivariate analysis\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"3\" nameend=\"c8\" namest=\"c6\"\u003e \u003cp\u003eMultivariate analysis\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVariables\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eHR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cp\u003e95% CI\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cem\u003eP\u003c/em\u003e-value\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eHR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e95% CI\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e\u003cem\u003eP\u003c/em\u003e-value\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge (years)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003e0.996\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.946\u0026ndash;1.049\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.891\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSex (male)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003e4.740\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.627\u0026ndash;13.815\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.004\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e4.526\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e1.560\u0026ndash;13.132\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.005\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLaterality (Right)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003e1.517\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.692\u0026ndash;3.323\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.298\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBaseline IOP (mmHg)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003e1.113\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.018\u0026ndash;1.218\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.019\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1.115\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e1.024\u0026ndash;1.214\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.012\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDuration of DM (years)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003e1.007\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.952\u0026ndash;1.064\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.817\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHbA1c (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003e0.997\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.768\u0026ndash;1.294\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.981\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCr (mg/dL)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003e0.682\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.440\u0026ndash;1.058\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.087\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePreoperative PRP\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003e1.816\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.749\u0026ndash;4.404\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.187\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIschemic stroke\u003c/p\u003e \u003cp\u003e(cardiac or cerebral)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003e1.121\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.141\u0026ndash;8.897\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.914\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSystemic hypertension\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003e0.728\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.329\u0026ndash;1.613\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.434\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIntraoperative tamponade\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003e0.633\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.230\u0026ndash;1.742\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.376\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFollow up period (months)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePostoperative IVB\u003c/p\u003e \u003cp\u003e(within 2 months)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003e0.179\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.042\u0026ndash;0.760\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.020\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.194\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.046\u0026ndash;0.815\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.025\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eCr, creatinine; CI, confidence interval; DM, diabetes mellitus; HbA1c, hemoglobin A1c; HR, hazard ratio; IOP, intraocular pressure; IVB, intravitreal bevacizumab; NVG, neovascular glaucoma; PRP, pan-retinal photocoagulation.\u003c/p\u003e \u003cp\u003eIn this study, no ocular or systemic side effects related to IVB, including systemic thromboembolic events or endophthalmitis, were observed. A total of 25 eyes (11.36%) experienced postoperative vitreous hemorrhage. Of these, 15 required vitrectomy. Tractional retinal detachment occurred in 19 eyes (8.63%) for which silicone oil tamponade was performed. Overall, 29 eyes (13.18%) developed NVG; in all these cases, IOP was controlled with maximum tolerated medical therapy. Glaucoma surgery was performed when intraocular pressure could not be controlled despite maximum tolerated medical therapy. Ahmed valve implantation was performed in seven eyes, and trabeculectomy was performed in another seven eyes. Intraocular pressure returned to normal in all cases after surgery. When comparing the number of IVB injections within 2 years after phacovitrectomy, the average was 1.27\u0026thinsp;\u0026plusmn;\u0026thinsp;1.77 injections in the group without NVG, and 3.17\u0026thinsp;\u0026plusmn;\u0026thinsp;2.95 injections in the group with NVG (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.002). The final BCVA was lower in the group with NVG compared to the group without NVG (0.05\u0026thinsp;\u0026plusmn;\u0026thinsp;1.95 vs 0.27\u0026thinsp;\u0026plusmn;\u0026thinsp;0.04, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001).\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eWe aimed to report the risk factors for NVG during phacovitrectomy and the utility of early postoperative IVB. The prevalence of NVG in this study was 13.18%, which is higher than that reported in recent studies.\u003csup\u003e\u003cspan additionalcitationids=\"CR8\" citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u003c/sup\u003e However, this incidence rate can vary depending on the surgical method, patient characteristics, and observation period. Our study involved a lengthy follow-up period of 49.69\u0026thinsp;\u0026plusmn;\u0026thinsp;22.29 months, and phacovitrectomy was performed on all patients. Although it is a somewhat older study, the incidence of NVG after vitrectomy in nonphakic eyes has been reported to be between 20% and 39%.\u003csup\u003e11\u0026ndash;13\u003c/sup\u003e Our team observed a higher incidence of NVG in patients undergoing phacovitectomy, and we confirmed that the group receiving IVB after surgery had a lower occurrence of postoperative NVG (16.67 vs 3.44%, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001).\u003c/p\u003e \u003cp\u003ePrevious studies conducted before the 1980s reported NVG incidence rates ranging 10\u0026ndash;23%, which decreased to 2\u0026ndash;15% after 1980s owing to advancements in equipment, enhanced surgical expertise, preoperative PRP, and the shift from pars plana lensectomy to phacoemulsification.\u003csup\u003e\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u003c/sup\u003e Aphakia was identified as the primary risk factor for NVG postvitrectomy in earlier studies, predominantly using the 20-gauge system and conventional surgical techniques while excluding patients who underwent lensectomy for aphakia. A meta-analysis of 5,161 patients from 26 studies conducted between 1993 and 2020 revealed a varied NVG incidence ranging 0.3\u0026ndash;23.6%; however,\u003csup\u003e\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e\u003c/sup\u003e the choice of gauge during surgery and the use of antiVEGF did not significantly impact NVG incidence; however, elevated preoperative IOP, combined preoperative or intraoperative cataract surgery, and postoperative VH were linked to a higher NVG incidence. In a previously conducted but unpublished study by our group comparing the vitrectomy-only group to the combined phacovitrectomy group in patients with PDR, the risk of NVG was higher in the phacovitectomy group (12.71%) than in the vitrectomy-only group (3.9%) (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.001).\u003c/p\u003e \u003cp\u003ePhacovitrectomy is increasingly performed nowadays because of its advantages, such as improving visibility during surgery\u003csup\u003e\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u003c/sup\u003e and addressing the issue of cataract worsening after vitrectomy in a single procedure.\u003csup\u003e\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u003c/sup\u003e However, noting the potential side effects of this surgery is always important. VEGF triggers the neovascularization of the iris, angle, and connective tissue membrane, leading to the subsequent formation of synechiae in the peripheral iris and trabecular meshwork.\u003csup\u003e\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e\u003c/sup\u003e In eyes that are both vitrectomized and lensectomized, the transport of oxygen, various growth factors, and cytokines through the vitreous cavity is accelerated.\u003csup\u003e\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e\u003c/sup\u003e Oxygen moves via diffusion and convection from the anterior chamber, where the partial pressure of oxygen is typically higher than at the retina, to the posterior segment of the eye. This oxygen movement results in hypoxia in the anterior segment and iris. Concurrently, growth factors, such as VEGF, are more efficiently transported from the retina to the iris. The combination of hypoxia in the anterior segment and the influx of additional VEGF from the retina promotes neovascularization of the iris, causing NVG. Conversely, in cases where only a vitrectomy is performed while preserving the lens, oxygen saturation within the retina tends to stabilize.\u003csup\u003e\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e\u003c/sup\u003e The surgery removes all neovascular and fibrovascular tissues, and the removal of the vitreous can aid in perfusing the remaining ischemic retina. Additionally, the vitreous is washed away; therefore, the concentration of VEGF within the vitreous significantly decreases compared to presurgery levels.\u003csup\u003e\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e\u003c/sup\u003e Therefore, a relatively lower likelihood of developing NVG is anticipated in these circumstances.\u003c/p\u003e \u003cp\u003eCataract surgery is known to trigger inflammation after the procedure, and studies have indicated that individuals diagnosed with NVG exhibit increased levels of inflammatory cytokines within the anterior chamber of the eye.\u003csup\u003e\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e\u003c/sup\u003e Moreover, studies have suggested that NVG is more prevalent in individuals with uveitis, implying that inflammation alone could increase the likelihood of NVG.\u003csup\u003e\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e\u003c/sup\u003e Another condition that can arise due to inflammation following the removal of the crystalline lens is pseudophakic cystoid macular edema (PCME), also known as Irvine\u0026ndash;Gass syndrome. This condition typically occurs 4\u0026ndash;6 weeks after surgery, with most cases developing within 3 months.\u003csup\u003e\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e\u003c/sup\u003e Topical NSAIDs can be used to prevent PCME. Recent studies have indicated that the incidence of PCME is higher in cases where combined phacovitrectomy is performed compared to vitrectomy alone in pseudophakic eyes.\u003csup\u003e\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e\u003c/sup\u003e This finding aligns with the results of this study, which shows a higher incidence of NVG following phacovitrectomy in patients with PDR. Furthermore, considering that the timing of PCME and NVG onset is similar, the early administration of postoperative bevacizumab could be further supported as a rationale for prevention.\u003c/p\u003e \u003cp\u003eAdministering bevacizumab, an anti-VEGF antibody, through intravitreal injection in patients with PDR, has been observed to quickly cause the regression of neovascularization in both the retina and iris.\u003csup\u003e\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e\u003c/sup\u003e Furthermore, reports suggest that administering bevacizumab before vitrectomy in cases of PDR can reduce intraoperative bleeding and facilitate surgery,\u003csup\u003e\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e\u003c/sup\u003e and that administering bevacizumab during surgery can lead to a reduction in VH after surgery.\u003csup\u003e\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e\u003c/sup\u003e However, no studies have demonstrated the effectiveness of preoperative or intraoperative bevacizumab in relation to postoperative NVG. In a study on the pharmacokinetics of IVB, bevacizumab administered via the intravitreal route could also be detected in the anterior chamber.\u003csup\u003e\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e\u003c/sup\u003e This suggests that administering bevacizumab intravitreally may contribute to lowering the concentration of VEGF in the anterior chamber, which could reduce the incidence of NVG. Two studies have discussed the relationship between postoperative anti-VEGF use and the incidence of NVG. Kwon et al.\u003csup\u003e\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e\u003c/sup\u003e reported that the use of bevacizumab after phacovitrectomy and vitrectomy (102 of 127 patients who underwent phacovitrectomy) increased the incidence of NVG. However, in their study, bevacizumab was only administered in cases of postoperative VH, making it challenging to determine whether the increase in NVG was due to postoperative VH or the injection of bevacizumab itself. Another study\u003csup\u003e\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e\u003c/sup\u003e suggested that postoperative administration of ranibizumab reduced the incidence of NVG. However, in this study, only 43.32% of cases involved phacovitrectomy. In our study, we observed a decrease in the incidence of NVG after phacovitrectomy when bevacizumab was administered within 2 months. Considering that the average onset time of NVG was 9.53\u0026thinsp;\u0026plusmn;\u0026thinsp;4.50 months, with the earliest case occurring at 2.5 months, we determined that administering bevacizumab within 2 months could be effective in preventing NVG.\u003c/p\u003e \u003cp\u003eMale sex and a high preoperative IOP increased the incidence of NVG. Several studies examining the incidence of NVG have reported a higher prevalence in males\u003csup\u003e\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e\u003c/sup\u003e. Studies have shown that the incidence of stroke is also higher in men than in women\u003csup\u003e\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e\u003c/sup\u003e; hence, it can be presumed that there is a clear sex predilection affecting the incidence of ischemia. Studies have confirmed the association between high preoperative IOP and a higher incidence of NVG. In our study, we also found that a high IOP before surgery increased the incidence of NVG\u003csup\u003e\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e\u003c/sup\u003e. Although neovascularization of the iris and angle was not detected in the preoperative examination, subtle NVG that was difficult to detect may have been present prior to surgery.\u003c/p\u003e \u003cp\u003eThe limitations of our study include its retrospective design. We were unable to measure or compare the actual concentrations of VEGF in the anterior chamber. Additionally, we were unable to directly measure and compare nonperfusion areas postoperatively. In future prospective studies, our research team intends to quantitatively measure preoperative and postoperative VEGF and cytokine levels as well as the nonperfusion area to demonstrate that NVG occurs more frequently after phacovitrectomy and that postoperative bevacizumab is useful in preventing NVG.\u003c/p\u003e \u003cp\u003eIn conclusion, our study revealed that male sex and a high preoperative IOP were associated with a higher incidence of NVG in patients with PDR undergoing phacovitrectomy. Additionally, administering IVB within 2 months of surgery can reduce the occurrence of NVG, and this approach is clinically beneficial.\u003c/p\u003e"},{"header":"Materials and Methods","content":"\u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003eStudy design\u003c/h2\u003e \u003cp\u003eThis retrospective observational case-control study enrolled patients with PDR who had phacovitrectomy for VH at a single tertiary medical center (Hanyang University Guri Hospital in South Korea) between January 2016 and January 2022. This retrospective study was approved by the Institutional Review Board of Hanyang University Guri Hospital (2023-12-023). All the procedures were performed in strict compliance with the ethical standards of the Declaration of Helsinki. The informed consent was waived by the Institutional Review Board of Hanyang University Guri Hospital because of the retrospective nature of the study.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003ePatient population\u003c/h3\u003e\n\u003cp\u003eWe collected data on all patients who underwent phacovitrectomy from the medical information team between 2016 and 2022 in a consecutive manner. At the request of the medical information team, we gathered a consecutive series of patients with diagnoses code including \u0026ldquo;PDR,\u0026rdquo; \u0026ldquo;tractional retinal detachment (tRD),\u0026rdquo; or \u0026ldquo;VH,\u0026rdquo; along with those who had a charge for \u0026ldquo;vitrectomy,\u0026rdquo; and \u0026ldquo;phacoemulsification.\u0026rdquo; The patient cohort comprised of individuals who underwent vitrectomy for conditions such as VH, tRD, and epiretinal membrane. We reviewed the medical records, and the exclusion criteria were as follows: eyes treated with vitrectomy due to any retinal diseases, received vitrectomy-only procedure, intraocular injection of triamcinolone acetonide, eyes with severe intraocular inflammation, a history of glaucoma or preoperative rubeosis, and lost to follow-up before the period of 2 years (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eEach patient's medical records encompassed comprehensive general and ocular histories and were thoroughly documented. These included detailed slit-lamp examinations, intraocular pressure (IOP) measurements, assessment of the best-corrected visual acuity (BCVA), evaluation of the presence or absence of preoperative panretinal photocoagulation (PRP), and identification of underlying systemic hypertension. Additionally, a history of cardiac or cerebral ischemic stroke was noted, along with the application of intraoperative tamponade. The follow-up period for all patients was extended beyond 1 year. Preoperative IVB was administered to all patients within 1 week prior to surgery.\u003c/p\u003e \u003cp\u003ePostoperative NVG was characterized by the presence of the anterior segment (the iris or angle) neovascularization, as identified through slit-lamp and gonioscopic examinations following vitrectomy. Additionally, a postoperative IOP exceeding 22 mmHg, confirmed during a subsequent visit, was also a defining criterion for NVG. All patients were followed up for a minimum of 2 years and the mean follow-up period was 49.69\u0026thinsp;\u0026plusmn;\u0026thinsp;22.29 months.\u003c/p\u003e\n\u003ch3\u003eSurgical techniques\u003c/h3\u003e\n\u003cp\u003eSurgery was performed by an experienced retinal surgeon (Y.U.S.) using a Constellation Vision System (Alcon Laboratories, Inc., Fort Worth, TX, USA) with wide-angle viewing using 23- or 25-gauge instruments. In each surgical case, phacoemulsification was performed before the vitreoretinal procedure. When intraocular lens (IOL) calculations were impeded by retinal detachments or VHs, axial length measurements were obtained using A-scan ultrasound. These measurements were corroborated with the full optical biometry of the unaffected contralateral eye. Following the completion of phacoemulsification and acrylic foldable IOL implantation via the primary 2.8-mm corneal incision in the posterior chamber, all viscoelastic substances were meticulously aspirated. To prevent the collapse of the anterior chamber during vitrectomy, a 10\u0026thinsp;\u0026minus;\u0026thinsp;0 nylon suture was placed on the clear corneal wound as a prophylactic measure. After cataract extraction, a standard 3-port 23- or 25-gauge pars plana vitrectomy was performed. The surgical procedure was concluded with fluid-air exchange and gas or silicone oil injections in scenarios where retinal breaks or retinal detachments were detected. Additionally, endolaser treatment was applied in all patients to complete panretinal photocoagulation. Postoperatively, all patients were prescribed topical antibiotics, which were administered four times daily for a duration of 2 weeks. Topical steroids were applied 4\u0026ndash;8 times daily, with a gradual reduction in frequency over time. Topical nonsteroidal anti-inflammatory drugs were also prescribed twice daily for a period of 2 months following surgery.\u003c/p\u003e \u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003eStatistical analysis\u003c/h2\u003e \u003cp\u003eData analysis was performed using the SPSS software, version 29.0 (IBM Corp., Armonk, NY, USA).\u003c/p\u003e \u003cp\u003eThe patients were divided into two groups for comparative analysis: one group received IVB within 2 months after surgery (Group 1), whereas the other group did not receive postoperative IVB within 2 months after surgery (Group 2). Initially, Group 1 consisted of 58 patients while Group 2 had 162 patients. To minimize demographic differences between the groups in this retrospective study, we conducted a propensity score matching, ensuring that age and sex distributions were balanced. We used the nearest neighbor method for matching in a 1:1 ratio. The effectiveness of this matching was assessed by calculating the absolute mean differences in the propensity scores.\u003c/p\u003e \u003cp\u003eIn the analysis of two-group comparisons, parametric variables were evaluated using Student's t-test, whereas nonparametric data were assessed using the Mann\u0026ndash;Whitney U test. For categorical data, Pearson\u0026rsquo;s chi-square test was employed, and in instances where any cell of a contingency table contained values less than five, Fisher\u0026rsquo;s exact test was used. Kaplan\u0026ndash;Meier survival analysis was used to ascertain the incidence of NVG following phacovitrectomy in patients with PDR. To identify risk factors and quantify their hazard ratios (HR) for the development of NVG postphacovitrectomy in patients with PDR, multivariate analysis using the Cox proportional hazards model was conducted. The analysis encompassed a range of potential risk factors, including patient sex, age, baseline IOP (defined as the average of three consecutive IOP measurements before vitrectomy), duration of diabetes, systemic hypertension, history of ischemic stroke (cardiac or cerebral), serum hemoglobin A1c levels, serum creatinine concentration, history of preoperative panretinal photocoagulation, use of gas or silicone oil tamponade during vitrectomy, and postoperative IVB within 2 months. Statistical significance was established at a \u003cem\u003eP\u003c/em\u003e-value threshold of \u0026lt;\u0026thinsp;0.05\u003c/p\u003e \u003c/div\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAuthorship contribution\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSunjin Hwang\u003c/strong\u003e: Writing – original draft, Writing – review \u0026amp; editing, Methodology, Data curation, Formal analysis. \u003cstrong\u003eEun Hee Hong\u003c/strong\u003e: Data curation, Formal analysis\u003cstrong\u003e. Min Ho Kang\u003c/strong\u003e: Data curation, Formal analysis. \u003cstrong\u003eYong Un Shin\u003c/strong\u003e: Conceptualization, Methodology, Writing – review \u0026amp; editing, Supervision.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgments\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe would like to thank Editage (www.editage.co.kr) for English language editing.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding/Support:\u003c/strong\u003e No specific grants from public, commercial, or non-profit funding agencies supported this research..\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDisclosure(s) :\u003c/strong\u003e All authors have completed and submitted the disclosures form.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThere are no conflicts of interest for any author.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData Availability\u003c/strong\u003e: The datasets used and/or analyzed in this study can be obtained from the corresponding author upon reasonable request.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eSong P, Yu J, Chan KY, Theodoratou E, Rudan I. Prevalence, risk factors and burden of diabetic retinopathy in China: a systematic review and meta-analysis. \u003cem\u003eJ Glob Health. \u003c/em\u003e2018;8(1).\u003c/li\u003e\n\u003cli\u003eKlein BE, Klein R, Moss SE. Incidence of cataract surgery in the Wisconsin Epidemiologic Study of Diabetic Retinopathy. \u003cem\u003eAm J Ophthalmol. \u003c/em\u003e1995;119(3):295-300.\u003c/li\u003e\n\u003cli\u003eBlankenship GW, Machemer R. Long-term diabetic vitrectomy results: report of 10 year follow-up. \u003cem\u003eOphthalmology. \u003c/em\u003e1985;92(4):503-506.\u003c/li\u003e\n\u003cli\u003eBraunstein RE, Airiani S. Cataract surgery results after pars plana vitrectomy. \u003cem\u003eCurr Opin Ophthalmol. \u003c/em\u003e2003;14(3):150-154.\u003c/li\u003e\n\u003cli\u003eSilva PS, Diala PA, Hamam RN, et al. Visual outcomes from pars plana vitrectomy versus combined pars plana vitrectomy, phacoemulsification, and intraocular lens implantation in patients with diabetes. \u003cem\u003eRetina (Philadelphia, Pa). \u003c/em\u003e2014;34(10):1960-1968.\u003c/li\u003e\n\u003cli\u003eXiao K, Dong Y-C, Xiao X-G, et al. Effect of pars plana vitrectomy with or without cataract surgery in patients with diabetes: a systematic review and meta-analysis. \u003cem\u003eDiab Ther. \u003c/em\u003e2019;10:1859-1868.\u003c/li\u003e\n\u003cli\u003eOshima Y, Shima C, Wakabayashi T, et al. Microincision vitrectomy surgery and intravitreal bevacizumab as a surgical adjunct to treat diabetic traction retinal detachment. \u003cem\u003eOphthalmology. \u003c/em\u003e2009;116(5):927-938.\u003c/li\u003e\n\u003cli\u003eLahey JM, Francis RR, Kearney JJ. Combining phacoemulsification with pars plana vitrectomy in patients with proliferative diabetic retinopathy: a series of 223 cases. \u003cem\u003eOphthalmology. \u003c/em\u003e2003;110(7):1335-1339.\u003c/li\u003e\n\u003cli\u003ePark DH, Shin JP, Kim SY. Intravitreal injection of bevacizumab and triamcinolone acetonide at the end of vitrectomy for diabetic vitreous hemorrhage: a comparative study. \u003cem\u003eGraef Arch Clin Exp Ophthalmol. \u003c/em\u003e2010;248:641-650.\u003c/li\u003e\n\u003cli\u003eWakabayashi Y, Usui Y, Okunuki Y, et al. Intraocular VEGF level as a risk factor for postoperative complications after vitrectomy for proliferative diabetic retinopathy. \u003cem\u003eInvest Ophthalmol Vis Sci. \u003c/em\u003e2012;53(10):6403-6410.\u003c/li\u003e\n\u003cli\u003eSummanen P. Neovascular glaucoma following vitrectomy for diabetic eye disease. \u003cem\u003eActa ophthalmologica. \u003c/em\u003e1988;66(1):110-116.\u003c/li\u003e\n\u003cli\u003eWand M, Madigan JC, Gaudio AR, Sorokanich S. Neovascular glaucoma following pars plana vitrectomy for complications of diabetic retinopathy. Vol 21: SLACK Incorporated Thorofare, NJ; 1990:113-118.\u003c/li\u003e\n\u003cli\u003eAaberg TM. Clinical results in vitrectomy for diabetic traction retinal detachment. \u003cem\u003eAm J Ophthalmol. \u003c/em\u003e1979;88(2):246-253.\u003c/li\u003e\n\u003cli\u003eSun D, Lin Y, Zeng R, Yang Z, Deng X, Lan Y. The incidence and risk factors of neovascular glaucoma secondary to proliferative diabetic retinopathy after vitrectomy. \u003cem\u003eEur J Ophthalmol. \u003c/em\u003e2021;31(6):3057-3067.\u003c/li\u003e\n\u003cli\u003eSooHoo JR, Seibold LK, Kahook MY. Recent advances in the management of neovascular glaucoma. Paper presented at: Seminars in ophthalmology2013.\u003c/li\u003e\n\u003cli\u003eStef\u0026aacute;nsson E. Physiology of vitreous surgery. \u003cem\u003eGraef Arch Clin Exp Ophthalmol. \u003c/em\u003e2009;247:147-163.\u003c/li\u003e\n\u003cli\u003eMaeda N, Tano Y. Intraocular oxygen tension in eyes with proliferative diabetic retinopathy with and without vitreous. \u003cem\u003eGraef Arch Clin Exp Ophthalmol. \u003c/em\u003e1996;234:S66-S69.\u003c/li\u003e\n\u003cli\u003eChen H-J, Ma Z-Z, Li Y, Wang C-G. Change of vascular endothelial growth factor levels following vitrectomy in eyes with proliferative Diabetic Retinopathy. \u003cem\u003eJ Ophthalmol. \u003c/em\u003e2019;2019.\u003c/li\u003e\n\u003cli\u003eSong S, Yu X, Zhang P, Dai H. Increased levels of cytokines in the aqueous humor correlate with the severity of diabetic retinopathy. \u003cem\u003eJ Diab Comp. \u003c/em\u003e2020;34(9):107641.\u003c/li\u003e\n\u003cli\u003eMohapatra A, Sudharshan S, Majumder PD, Sreenivasan J, Raman R. Clinical profile and ocular morbidities in patients with both Diabetic Retinopathy and Uveitis. \u003cem\u003eOphthalmol Sci. \u003c/em\u003e2024:100511.\u003c/li\u003e\n\u003cli\u003eYonekawa Y, Kim IK. Pseudophakic cystoid macular edema. \u003cem\u003eCurr Opi Ophthalmol. \u003c/em\u003e2012;23(1):26-32.\u003c/li\u003e\n\u003cli\u003ePark SW, Kim HK, Zaidi MH, Byon IS, Lee JE, Nguyen QD. Cystoid macular edema after vitrectomy and after phacovitrectomy for epiretinal membrane. \u003cem\u003eCan J Ophthalmol. \u003c/em\u003e2023.\u003c/li\u003e\n\u003cli\u003eAvery RL, Pearlman J, Pieramici DJ, et al. Intravitreal bevacizumab (Avastin) in the treatment of proliferative diabetic retinopathy. \u003cem\u003eOphthalmology. \u003c/em\u003e2006;113(10):1695-1705. e1696.\u003c/li\u003e\n\u003cli\u003eLucena DR, Ribeiro JA, Costa RA, et al. Intraoperative bleeding during vitrectomy for diabetic tractional retinal detachment with versus without preoperative intravitreal bevacizumab (IBeTra study). \u003cem\u003eBr J Ophthalmol. \u003c/em\u003e2009.\u003c/li\u003e\n\u003cli\u003eAhn J, Woo SJ, Chung H, Park KH. The effect of adjunctive intravitreal bevacizumab for preventing postvitrectomy hemorrhage in proliferative diabetic retinopathy. \u003cem\u003eOphthalmology. \u003c/em\u003e2011;118(11):2218-2226.\u003c/li\u003e\n\u003cli\u003eBakri SJ, Snyder MR, Reid JM, Pulido JS, Singh RJ. Pharmacokinetics of intravitreal bevacizumab (Avastin). \u003cem\u003eOphthalmology. \u003c/em\u003e2007;114(5):855-859.\u003c/li\u003e\n\u003cli\u003eKwon J-w, Jee D, La TY. Neovascular glaucoma after vitrectomy in patients with proliferative diabetic retinopathy. \u003cem\u003eMedicine. \u003c/em\u003e2017;96(10).\u003c/li\u003e\n\u003cli\u003eLiang X, Zhang Y, Li Y-P, Huang W-R, Wang J-X, Li X. Frequency and risk factors for neovascular glaucoma after vitrectomy in eyes with diabetic retinopathy: an observational study. \u003cem\u003eDiab Ther. \u003c/em\u003e2019;10:1801-1809.\u003c/li\u003e\n\u003cli\u003eGoto A, Inatani M, Inoue T, et al. Frequency and risk factors for neovascular glaucoma after vitrectomy in eyes with proliferative diabetic retinopathy. \u003cem\u003eJ Glaucoma. \u003c/em\u003e2013;22(7):572-576.\u003c/li\u003e\n\u003cli\u003eAppelros P, Stegmayr B, Ter\u0026eacute;nt A. Sex differences in stroke epidemiology: a systematic review. \u003cem\u003eStroke. \u003c/em\u003e2009;40(4):1082-1090. \u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"scientific-reports","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"scirep","sideBox":"Learn more about [Scientific Reports](http://www.nature.com/srep/)","snPcode":"","submissionUrl":"","title":"Scientific Reports","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Scientific Reports","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Phacovitrectomy, Neovascular glaucoma, Prevention, Bevacizumab","lastPublishedDoi":"10.21203/rs.3.rs-5214895/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-5214895/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003ePurpose\u003c/h2\u003e \u003cp\u003eTo evaluate the effectiveness of postoperative intravitreal bevacizumab (IVB) in preventing neovascular glaucoma (NVG) and identify associated risk factors in patients with proliferative diabetic retinopathy (PDR) undergoing phacovitrectomy.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003ePatients with PDR who underwent phacovitrectomy were enrolled and categorized into two subgroups based on their postoperative treatment regimen: one group received IVB within 2 months following phacovitrectomy (Group 1); the other did not receive IVB during this period (Group 2). A comparative analysis evaluated the distinguishing characteristics of the two groups after 1:1 propensity score matching. Kaplan\u0026ndash;Meier survival analysis was utilized to determine the incidence of NVG after phacovitrectomy. Multivariate analysis with the Cox proportional hazards model identified risk factors associated with NVG postphacovitrectomy.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eA total of 220 eyes of 220 patients were investigated in this study. NVG developed in 29 eyes (13.18%). The probabilities of NVG occurrence at 6, 12, and 24 months following phacovitrectomy were 2.72%, 5.45%, and 13.18%, respectively. When comparing Groups 1 (n\u0026thinsp;=\u0026thinsp;58) and 2 (n\u0026thinsp;=\u0026thinsp;58), a significant difference was observed in the occurrence of NVG (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001). In Group 1, only two cases of NVG (3.44%) were noted, whereas all other NVG cases occurred in Group 2 (16.67%). Male sex and high preoperative intraocular pressure (IOP) were associated with NVG occurrence following phacovitrectomy, and the administration of IVB within 2 months postphacovitrectomy demonstrated efficacy in preventing the development of NVG.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eMale sex and high preoperative IOP were associated with a higher incidence of NVG, and postoperative IVB had a protective effect against NVG occurrence.\u003c/p\u003e","manuscriptTitle":"Early Postoperative Bevacizumab for Preventing Neovascular Glaucoma in Phacovitrectomy for Proliferative Diabetic Retinopathy","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-12-03 23:38:02","doi":"10.21203/rs.3.rs-5214895/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2024-11-18T06:05:33+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-11-17T16:50:31+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-10-26T03:15:54+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-10-26T01:49:44+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"331423870545461480420681851328920251009","date":"2024-10-20T14:59:47+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"152325663906110939586156572515683053739","date":"2024-10-15T12:34:41+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"49173276292457680898789976513891774415","date":"2024-10-13T11:56:47+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2024-10-13T11:47:59+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2024-10-13T11:43:50+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2024-10-08T04:21:12+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2024-10-07T05:08:35+00:00","index":"","fulltext":""},{"type":"submitted","content":"Scientific Reports","date":"2024-10-07T02:18:15+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"scientific-reports","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"scirep","sideBox":"Learn more about [Scientific Reports](http://www.nature.com/srep/)","snPcode":"","submissionUrl":"","title":"Scientific Reports","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Scientific Reports","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"f9ed6bce-bd55-4118-84e9-dac92b65d505","owner":[],"postedDate":"December 3rd, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[{"id":40381113,"name":"Health sciences/Medical research/Outcomes research"},{"id":40381114,"name":"Health sciences/Risk factors"}],"tags":[],"updatedAt":"2025-01-13T16:03:30+00:00","versionOfRecord":{"articleIdentity":"rs-5214895","link":"https://doi.org/10.1038/s41598-025-85667-y","journal":{"identity":"scientific-reports","isVorOnly":false,"title":"Scientific Reports"},"publishedOn":"2025-01-07 15:57:46","publishedOnDateReadable":"January 7th, 2025"},"versionCreatedAt":"2024-12-03 23:38:02","video":"","vorDoi":"10.1038/s41598-025-85667-y","vorDoiUrl":"https://doi.org/10.1038/s41598-025-85667-y","workflowStages":[]},"version":"v1","identity":"rs-5214895","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-5214895","identity":"rs-5214895","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}