Intraocular Pressure Elevation Following Vitreoretinal Surgery - A Prospective Cohort Study

Intraocular Pressure Elevation Following Vitreoretinal Surgery - A Prospective Cohort Study | 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 Research Article Intraocular Pressure Elevation Following Vitreoretinal Surgery - A Prospective Cohort Study Preeti Agarwal, Madhu Thapa, Pratap Karki This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-9509509/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 10 You are reading this latest preprint version Abstract Background Increase in IOP after Vitreoretinal surgery is uncommon but sight threatening complication. This study aims to determine the incidence and risk factors of intraocular pressure (IOP) elevation following vitreoretinal surgery. Methods A prospective, hospital-based observational cohort study was conducted at BPKLCOS, Kathmandu, Nepal (February 2019 – February 2020). Forty-six eyes of 42 patients undergoing primary vitreoretinal surgery were enrolled. IOP was measured by Goldmann applanation tonometry pre-operatively and on post-operative days 1, 7, and 30 (POD1, POD7, POD30). Anterior chamber angle (ACA) and depth (ACD) were quantified using the Sirius Scheimpflug-Placido topographer at baseline and POD30. Statistical analysis employed the Friedman test and Wilcoxon signed-rank test for non-normal data (IOP, ACD) and paired t-test with one-way ANOVA for normally distributed data (ACA). Results Mean age of the study population was 52.61 ± 17.23 years; male-to-female ratio 1.8:1. IOP rose significantly on POD1 (median 17 vs. 15 mmHg; p = 0.006) and declined by POD30 (median 13 mmHg; p value 0.001 vs. POD1). The Band Buckle + Silicon Oil (BB + SOI) group showed the greatest IOP elevation (overall p value 0.023; POD1 p value 0.018). Rhegmatogenous retinal detachment (RRD) was the diagnosis most significantly associated with sustained IOP elevation (overall p value 0.009; POD1 p value 0.007). Intraoperative endolaser was independently associated with IOP rise (p = 0.009). Male patients showed statistically significant overall IOP elevation (Friedman χ² = 11.885; p value 0.008). ACA did not change significantly (p value 0.363), ACD increased significantly at POD30 (mean + 0.19 mm; p value 0.020). Conclusion Post-vitrectomy IOP elevation peaks on POD1 and gradually decreases over the time. This is most pronounced in eyes undergoing RRD repair with BB + SOI and those receiving intraoperative endolaser. Although ACA does not change but ACD deepened which was statistically significant. Anterior chamber Endolaser Intraocular pressure Pars plana vitrectomy Rhegmatogenous retinal detachment Scleral buckle Silicone oil Figures Figure 1 Background Vitreoretinal surgery has advanced considerably over past few decades, improving the safety and expanding its role in managing complex posterior segment diseases. Intraocular-pressure (IOP) elevation remains a potentially vision-threatening postoperative complication. Reported incidence rates vary widely, from 3.6% to 22.2% in general vitreoretinal series, with rates of up to 40% recorded within the first 48 hours in gas-tamponade procedures[ 1 , 2 , 3 ]. Acute elevation of IOP can cause central retinal artery occlusion, retinal vein occlusion, optic nerve head ischemia and macular infarction. Chronic IOP elevation leads progressive glaucomatous optic neuropathy. Several risk factors, including the type of intraocular tamponade, primary retinal diagnosis, and use of intraoperative laser photocoagulation[ 4 , 5 , 6 ]. Similar to increasing global literature, Nepal also carries a significant burden of diabetic retinopathy, rhegmatogenous retinal detachment, and vascular occlusive disease, creating a high-risk vitreoretinal surgical population. The present study was therefore designed to prospectively characterize IOP changes following vitreoretinal surgery at a major tertiary. Methods This was a prospective, hospital-based, observational cohort study conducted at the Retina and Glaucoma Clinic of B.P. Koirala Lions Centre for Ophthalmic Studies (BPKLCOS), Maharajgunj Medical Campus, Institute of Medicine, Tribhuvan University, Kathmandu, Nepal, from February 2019 to February 2020. Ethical approval for the study was obtained from Institutional Review committee approval was obtained, and written informed consent was secured from all participants prior to enrolment. Consecutive patients undergoing primary vitreoretinal surgery were enrolled by purposive sampling. Inclusion criteria included patients over 18years to be scheduled for primary vitreoretinal surgery at BPKLCOS. Exclusion criteria comprised of pre-existing glaucoma or ocular hypertension, neovascular glaucoma, active uveitis, penetrating or open globe injury, blunt ocular trauma with documented angle damage, previous vitreoretinal surgery in the study eye and intraocular infection. A total of 46 eyes of 42 patients met these criteria and completed the study protocol. All procedures were performed by experienced vitreoretinal surgeons using 20-gauge or small-gauge (23G/25G) PPV systems. Tamponade selection of C3F8 gas, silicon oil (SOI), air, or Band Buckle combined with silicon oil (BB + SOI) was made at the operating surgeon's discretion based on the primary diagnosis and intraoperative findings. Intraoperative endolaser photocoagulation was applied when clinically indicated. The primary outcome was IOP measured by Goldmann applanation tonometry (GAT) at four time points: pre-operatively (baseline), and on POD1, POD7, and POD30. Secondary outcomes were anterior chamber angle (ACA) and anterior chamber depth (ACD), both assessed using the Sirius Scheimpflug-Placido topographer (Costruzione Strumenti Oftalmici, Italy) at baseline and POD30. Statistical Analysis Data were analysed using SPSS v23. Normality was assessed by Kolmogorov-Smirnov and Shapiro-Wilk tests. IOP and ACD were non-normally distributed and analysed with the Friedman test (overall group comparison) and Wilcoxon signed-rank test (pairwise post-hoc). ACA was normally distributed and analysed with paired t-test and one-way ANOVA. Statistical significance was set at p < 0.05. Results Demographic and Clinical Characteristics Of 102 vitreoretinal procedures performed during the study period, 46 eyes of 42 patients fulfilled inclusion criteria. Mean ± SD age was 52.61 ± 17.23 years (range 19–78 years); 39.13% of eyes were from patients in the 61–80 year age, and 36.95% from patients aged 41–60 years. The cohort was male-predominant (30 eyes, 65.21%; male-to-female ratio 1.8:1). Among systemic comorbidities, hypertension was present in 19.6%, diabetes mellitus in 17.4%, and both in 15.2% of cases, yielding a combined systemic vascular comorbidity burden of 52.2%. The most common retinal diagnoses were vitreous haemorrhage (VH) and rhegmatogenous retinal detachment (RRD), each accounting for 19.56% (n = 9) of eyes, followed by proliferative diabetic retinopathy (PDR, 17.39%, n = 8), and branch retinal vein occlusion (BRVO, 13.04%, n = 6). Pars plan vitrectomy with Silicon oil insertion (SOI) was the most frequently used tamponade (43.47%, n = 20), followed by C3F8 (30.43%, n = 14), BB + SOI (15.21%, n = 7), and air (10.86%, n = 5). Intraoperative endolaser was performed in 60.87% of eyes (n = 28). IOP by Tamponade Group After Pars plana vitrectomy, internal tamponade was done using various substances like Silicon oil, expending gases like C3F8, air and external tamponade was done using belt and buckle. Table 2 IOP dynamics stratified by tamponade group Tamponade n (%) Friedman χ² Overall p value POD1 vs Pre-op p value Silicon Oil (SOI) 20 (43.5%) 5.19 0.159 0.247 C3F8 Gas 14 (30.4%) 5.41 0.144 0.169 Air 5 (10.9%) 8.25 0.051 0.680 Band Buckle + SOI (BB + SOI) 7 (15.2%) 9.49 0.023 0.018 (Friedman test and Wilcoxon post-hoc)* Statistically significant (p < 0.05). Only the BB + SOI group demonstrated a statistically significant overall IOP variation across the four time points (Friedman χ² = 9.49; p value 0.023). Within this group, POD1 IOP was significantly higher than the pre-operative baseline (Wilcoxon p value 0.018), and a significant decline from POD1 to POD30 was confirmed (p value 0.046). No other tamponade group achieved overall statistical significance SOI (p value 0.159), C3F8 (p value 0.144), and air (p value 0.051) as shown in Table 2 . IOP by Primary Retinal Diagnosis Table 3 IOP dynamics stratified by primary retinal diagnosis (Friedman test with Wilcoxon post-hoc) Diagnosis n (%) χ² Overall P value POD1 vs Pre-op P value Vitreous Hemorrhage (VH) 9 (19.6%) 1.08 0.783 0.888 Rhegmatogenous RD (RRD) 9 (19.6%) 11.63 0.009 0.007 Proliferative DR (PDR) 8 (17.4%) 6.80 0.078 0.042 Branch RVO (BRVO) 6 (13.0%) 4.50 0.212 0.684 Central RVO (CRVO) 3 (6.5%) 8.25 0.051 0.102 FTMH / Other 11 (23.9%) — NS NS * Statistically significant (p < 0.05). RD = retinal detachment; PDR = proliferative diabetic retinopathy; RVO = retinal vein occlusion; FTMH = full-thickness macular hole; NS = not significant. Among diagnostic subgroups, only the RRD group demonstrated a statistically significant overall IOP variation (Friedman χ² = 11.625; p value 0.009). Post-hoc Wilcoxon analysis confirmed a significant rise on POD1 versus baseline (Z = − 2.675; p value 0.007), on POD7 versus POD1 (p value 0.028), and on POD30 versus POD1 (p value 0.035), indicating a sustained period of IOP elevation in RRD eyes extending beyond the first post-operative day. A trend toward IOP elevation on POD1 was observed in the PDR group (p value0.042) that did not achieve overall Friedman significance (p value 0.078) as shown in Table 3 . Endolaser and IOP In eyes that received intraoperative endolaser photocoagulation (n = 28), the overall Friedman test revealed a statistically significant IOP variation across the four time points (χ² = 11.543; p value 0.009). In contrast, no significant variation was observed in eyes that did not receive endolaser (n = 18; Friedman p value 0.280), identifying intraoperative laser photocoagulation as an independent contributor to post-operative IOP elevation. Anterior Chamber changes Table 4 Anterior chamber angle and depth: pre-operative versus post-operative Day 30 Parameter Pre-operative Post-operative (Day 30) p value AC Angle (mean ° ± SD) 34.02 ± 7.36 35.28 ± 7.42 0.363 (NS) AC Depth (median mm ± SD) 3.24 ± 0.52 3.41 ± 0.60 0.020* * Wilcoxon signed-rank test (ACD). Paired t-test (ACA). NS = not significant; SD = standard deviation. The AC angle did not change significantly between baseline and POD30 (mean increase 1.26 ± 9.30°; paired t-test p value 0.363). One-way ANOVA confirmed no significant difference in AC angle across tamponade subgroups at either baseline (p value 0.560) or POD30 (p value 0.353). In contrast, ACD increased significantly from a median of 3.24 ± 0.52 mm pre-operatively to 3.41 ± 0.60 mm at POD30 (Wilcoxon p value 0.020), corresponding to a mean increase of 0.19 ± 0.59 mm. No significant ACD change was observed within any individual tamponade subgroup (all p > 0.05) as shown in Table 4 . Discussion This prospective observational study provides structured longitudinal data on IOP dynamics and anterior chamber changes following vitreoretinal surgery in a South Asian tertiary care context, enrolling 46 eyes across a one-year period. The central findings is a significant POD1 IOP peak, greatest in the BB + SOI and RRD subgroups, and independently associated with endolaser application—are broadly consistent with the global literature, while the anterior segment morphometric data offer mechanistic insight that informs clinical management. The pattern of IOP elevation, peaking on POD1 and resolving to sub-baseline levels by POD30, mirrors findings reported by Framme et al[ 5 ]. (mean IOP 19.7 ± 8.0 mmHg at 24 hours post-20G PPV) and Desai et al[ 1 ]. (majority of elevations occurring within the first post-operative day). Multiple overlapping mechanisms operate in this acute window: inflammatory trabeculitis impairs trabecular outflow within hours of surgical manipulation; fibrinous anterior chamber reaction can produce pupillary membrane and secondary angle obstruction; choroidal congestion from endolaser or vortex vein compression causes forward rotation of the lens-iris diaphragm; and expanding gas tamponade volumetrically compresses the angle. By POD7, resolution of acute inflammation—aided by topical corticosteroid therapy—and partial gas resorption collectively restore outflow facility. The sub-baseline IOP observed at POD30 likely reflects the well-described long-term IOP-lowering effect of vitrectomy, postulated to result from improved posterior segment convection, enhanced uveoscleral outflow following vitreous removal, or subtle reduction in ciliary body secretory activity[ 7 ]. The exclusive statistical significance of the BB + SOI group among tamponade subgroups (overall p value 0.023) is mechanistically coherent. The encircling scleral band compresses the vortex veins, impairing choroidal venous drainage and triggering ciliary body engorgement and anterior rotation, thereby narrowing or closing the trabecular angle. Silicon oil adds a second independent mechanism: in aphakic or pseudophakic eyes with a disrupted posterior capsule, oil may migrate anteriorly to block the pupil or angle directly, while emulsified oil droplets and oil-laden macrophages obstruct the trabecular meshwork over time[ 8 ]. The absence of significant IOP elevation in the SOI-alone, C3F8, and air groups contrasts with findings from Xu et al[ 9 ]. and Framme et al[ 5 ], and is most likely attributable to the small intra-subgroup sample sizes limiting statistical power, combined with the expertise-related reduction in gas overfill and careful oil volume calibration by experienced surgeons at BPKLCOS. The persistent and significant IOP elevation in the RRD subgroup across POD1 through POD30 (p value 0.007, 0.028, and 0.035, respectively) reflects the complexity of RRD management at this centre: all RRD cases received silicon oil, the majority underwent endolaser, and a proportion required scleral buckling—thus concentrating multiple risk factors within this diagnostic category. The underlying pathophysiology is further compounded by the marked inflammatory response to longstanding retinal detachment, characterised by elevated aqueous flare, breakdown of the blood-retinal barrier, and trabecular obstruction by dispersed retinal pigment epithelial cells and inflammatory debris[ 10 ]. Pillai et al[ 11 ] similarly identified RD as the diagnostic category with the highest risk of post-operative IOP elevation (49.2% of eyes), while Kovacic et al[ 12 ]. confirmed retinal detachment as an independent predictor of greater IOP increase following PPV. Endolaser photocoagulation was identified as an independent risk factor in the present study (Friedman p = 0.009 in laser-treated versus p = 0.280 in untreated eyes). Laser-induced prostaglandin release stimulates uveoscleral outflow reduction, while choroidal oedema secondary to photocoagulation causes anterior displacement of the lens-iris diaphragm. These mechanisms are well-characterised in the laser literature and have direct implications for perioperative management: consideration should be given to prophylactic topical carbonic anhydrase inhibitors or beta-blockers at the conclusion of procedures involving extensive endolaser. The absence of a significant change in AC angle at POD30 (p = 0.363), coupled with the lack of tamponade-specific angle differences, strongly supports the predominance of open-angle mechanisms in this cohort—consistent with the conclusions of Chang[ 13 ] and Mansukhani et al[ 14 ] both of whom identified open-angle glaucoma, rather than angle-closure, as the characteristic long-term glaucomatous complication of vitreoretinal surgery. This mechanistic insight favours the use of aqueous suppressants over miotics for acute IOP management in the post-vitrectomy setting. The significant increase in ACD at POD30 (+ 0.19 mm; p = 0.020) is an apparently paradoxical finding in a setting where forward displacement of the lens-iris diaphragm by tamponade agents might be expected to shallow the anterior chamber. This observation is likely explained by the one-month interval of the measurement: by POD30, gas has largely resorbed (SF6 within 10–14 days; C3F8 by 6–8 weeks), choroidal congestion has resolved, and the posterior vitreous traction that previously displaced the lens anteriorly has been relieved by the vitrectomy itself. A comparison of immediate post-operative ACD (not measured in this study) with the POD30 value would be needed to determine whether an initial shallowing—as documented by Neudorfer et al[ 15 ] preceded the deepening observed at one month. Conclusion Post-vitrectomy IOP elevation is a predominantly early phenomenon that peaks on POD1 and resolves to sub-baseline values by one month in the majority of patients. The BB + SOI tamponade combination, RRD as the underlying diagnosis, and intraoperative endolaser photocoagulation each independently increase the risk of significant post-operative IOP elevation. The open-angle mechanism predominates, as evidenced by the absence of significant post-operative change in the anterior chamber angle. These findings support the implementation of structured, risk-stratified IOP monitoring protocols in vitreoretinal surgical programmes, with targeted prophylactic anti-glaucoma therapy in high-risk subgroups to prevent potentially irreversible glaucomatous sequelae. Limitation The relatively small sample size limits statistical power for subgroup analyses and precludes robust multivariate modeling of independent risk factors. The short follow-up period (30 days) does not capture delayed-onset glaucoma, particularly in silicone oil–filled eyes. Additionally, variability in surgical technique and tamponade selection introduces potential confounding. Future studies with larger cohorts, longer follow-up, and multivariate regression analysis are warranted. Abbreviations ACA: Anterior chamber angle ACD: Anterior Chamber depth BB: Band Buckle BRVO: Branch retinal vein occlusion CRVO: central retinal vein occlusion FTMH: full thickness macular hole IOP: Intra ocular pressure POD: Post-operative day PDR: Proliferative Diabetic retinopathy RRD: Rhegmatogenous retinal detachment SOI: Silicon Oil Vitreous Haemorrhage (VH) Declarations Ethical approval Was obtained from the ethics committee of Institutional Review Committee of Institute of Medicine , Tribhuvan University , Kathmandu, Nepal with the Reference number of 341(6-11) E2 in accordance with the Declaration of Helsinki. Human ethics/ Consent to Participate: The authors certify that INFORMED CONSENT were obtained from all the patients who participated in the study. Consent for publication: This is not applicable here. Data availability: The data used to support the findings of this study are available from the corresponding author upon a request. Acknowledgements: Not applicable. Competing interests: There is not competing interest in publication of this research. Funding: There is not funding received for this study. Authors' contributions: PA and PK collected data. MT, PK and PA did data analysis and prepared the figures and tables. PA wrote the main manuscript. MT and PK reviewed the manuscript. References Desai UR, Alhalel AA, Schiffman RM, Campen TJ, Sundar G, Muhich A. Intraocular pressure elevation after simple pars plana vitrectomy. Ophthalmology. 1997;104(5):781–6. 10.1016/S0161-6420(97)30229-6 . Anderson NG, Fineman MS, Brown GC. Incidence of intraocular pressure spike and other adverse events after vitreoretinal surgery. Ophthalmology. 2006;113(1):42–7. 10.1016/j.ophtha.2005.09.019 . Han DP, Lewis H, Lambrou FH, Mieler WF, Hartz A. Mechanisms of intraocular pressure elevation after pars plana vitrectomy. Ophthalmology. 1989;96(9):1357–62. 10.1016/S0161-6420(89)32678-9 . Hasegawa Y, Okamoto F, Sugiura Y, Okamoto Y, Hiraoka T, Oshika T. Intraocular pressure elevation after vitrectomy for various vitreoretinal disorders. Eur J Ophthalmol. 2014;24(2):235–41. 10.5301/ejo.5000360 . Framme C, Klotz S, Wolf-Schnurrbusch UEK, Wiedemann P, Wolf S. Intraocular pressure changes following 20G pars-plana vitrectomy. Acta Ophthalmol. 2012;90(8):744–9. 10.1111/j.1755-3768.2011.02153.x . Muether PS, Hoerster R, Kirchhof B, Fauser S. Course of intraocular pressure after vitreoretinal surgery. Retina. 2011;31(10):2035–42. 10.1097/IAE.0b013e318201a3de . Aaberg TM, Van Horn DL. Late complications of pars plana vitreous surgery. Ophthalmology. 1978;85(2):126–40. 10.1016/S0161-6420(78)35579-0 . Henderer JD, Budenz DL, Flynn HW Jr, Schiffman JC, Feuer WJ, Murray TG. Elevated intraocular pressure and hypotony following silicone oil retinal tamponade. Arch Ophthalmol. 1999;117(2):189–95. 10.1001/archopht.117.2.189 . Xu P, Xia T, Chen J. Early postoperative intraocular pressure elevation after vitreoretinal surgery. J Clin Exp Ophthalmol. 2017;8(2):631. 10.4172/2155-9570.1000631 . Matsumoto M, Yoshida S, Shichi H. Changes in aqueous flare intensity in rhegmatogenous retinal detachment. Jpn J Ophthalmol. 1994;38(4):412–6. Pillai GS, Varkey R, Unnikrishnan UG, Radhakrishnan N. Incidence and risk factors for intraocular pressure rise after transconjunctival vitrectomy. Indian J Ophthalmol. 2020;68(5):812–8. 10.4103/ijo.IJO_1523_19 . Kovacic H, Wolfs RCW, Kilic E, Ramdas WD. The effect of multiple vitrectomies and its indications on intraocular pressure. BMC Ophthalmol. 2019;19(1):175. 10.1186/s12886-019-1189-z . Chang S. LXII Edward Jackson Lecture: open angle glaucoma after vitrectomy. Am J Ophthalmol. 2006;141(6):1033–43. 10.1016/j.ajo.2006.01.060 . Mansukhani SA, Barkmeier AJ, Bakri SJ, et al. The risk of primary open-angle glaucoma following vitreoretinal surgery. Am J Ophthalmol. 2018;193:143–55. 10.1016/j.ajo.2018.06.012 . Neudorfer M, Oren N, Barak A. High-frequency ultrasound biomicroscopy of the anterior segment morphometry before and immediately after pars plana vitrectomy. Eur J Ophthalmol. 2011;21(2):173–8. 10.5301/EJO.2010.6081 . Thapa SS, Thapa R, Paudyal I, et al. Prevalence and pattern of vitreo-retinal diseases in Nepal: the Bhaktapur glaucoma study. BMC Ophthalmol. 2013;13:9. 10.1186/1471-2415-13-9 . Gedde SJ. Management of glaucoma after retinal detachment surgery. Curr Opin Ophthalmol. 2002;13(2):103–9. 10.1097/00055735-200204000-00008 . Ghomi Z, Ghassemi F. Changes in anterior segment parameters following pars plana vitrectomy measured by ultrasound biomicroscopy. Med Hypothesis Discov Innov Ophthalmol. 2017;6(3):76–81. 10.51329/mehdiophthal176 . Additional Declarations No competing interests reported. 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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-9509509","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":635901609,"identity":"03f3302f-10e8-49e8-918a-07ddfbc5ea02","order_by":0,"name":"Preeti Agarwal","email":"","orcid":"","institution":"Biratnagar Eye Hospital","correspondingAuthor":false,"prefix":"","firstName":"Preeti","middleName":"","lastName":"Agarwal","suffix":""},{"id":635901633,"identity":"718445c7-bc38-42ad-ae69-ae1fab68ff00","order_by":1,"name":"Madhu Thapa","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA70lEQVRIiWNgGAWjYDCCA0DM28DAYADifABiNnYitUiAtDDOAGlhJkULMw9IhJAWvtunEz+83XG4zpz97MHPNr+2yfMxMzB++JiDW4vkudzNknPPHJaw7MlLls7tu23YxszALDlzG24tBmd4N0jzth2WMDiQYyCd23ObEaiFjZkXv5bNv8Fazr8x/m3Zc9ueGC3bILbcyDGTZvhxO5GgFkmgFsu5bemSG268S7Psbbid3MbM2IzXL3xAh91422bNb3A+9/CNH39u285vbz744SMeLUgAGCmMbSAGYwNR6iFaGP4Qq3gUjIJRMApGEgAARJVVUBRmxlIAAAAASUVORK5CYII=","orcid":"","institution":"Institute of Medicine","correspondingAuthor":true,"prefix":"","firstName":"Madhu","middleName":"","lastName":"Thapa","suffix":""},{"id":635901653,"identity":"7bb7c44b-d584-493f-baf9-8c5b36788259","order_by":2,"name":"Pratap Karki","email":"","orcid":"","institution":"Institute of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Pratap","middleName":"","lastName":"Karki","suffix":""}],"badges":[],"createdAt":"2026-04-23 17:39:34","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-9509509/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-9509509/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":108974420,"identity":"8531b6bb-dacc-4383-b6a6-a2f58d107fce","added_by":"auto","created_at":"2026-05-11 10:51:12","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":62165,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eGraph showing mean IOP measurement at across four time points.\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"floatimage1.png","url":"https://assets-eu.researchsquare.com/files/rs-9509509/v1/c36c9ae4aff3799a817fbd29.png"},{"id":108974458,"identity":"eedec8f2-cf85-41e5-b04e-cb53cabf38ce","added_by":"auto","created_at":"2026-05-11 10:51:24","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":267157,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-9509509/v1/ec713a07-06ac-4564-ab44-b2ec2f92971a.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Intraocular Pressure Elevation Following Vitreoretinal Surgery - A Prospective Cohort Study","fulltext":[{"header":"Background","content":"\u003cp\u003eVitreoretinal surgery has advanced considerably over past few decades, improving the safety and expanding its role in managing complex posterior segment diseases. Intraocular-pressure (IOP) elevation remains a potentially vision-threatening postoperative complication. Reported incidence rates vary widely, from 3.6% to 22.2% in general vitreoretinal series, with rates of up to 40% recorded within the first 48 hours in gas-tamponade procedures[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eAcute elevation of IOP can cause central retinal artery occlusion, retinal vein occlusion, optic nerve head ischemia and macular infarction. Chronic IOP elevation leads progressive glaucomatous optic neuropathy. Several risk factors, including the type of intraocular tamponade, primary retinal diagnosis, and use of intraoperative laser photocoagulation[\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eSimilar to increasing global literature, Nepal also carries a significant burden of diabetic retinopathy, rhegmatogenous retinal detachment, and vascular occlusive disease, creating a high-risk vitreoretinal surgical population. The present study was therefore designed to prospectively characterize IOP changes following vitreoretinal surgery at a major tertiary.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003eThis was a prospective, hospital-based, observational cohort study conducted at the Retina and Glaucoma Clinic of B.P. Koirala Lions Centre for Ophthalmic Studies (BPKLCOS), Maharajgunj Medical Campus, Institute of Medicine, Tribhuvan University, Kathmandu, Nepal, from February 2019 to February 2020. Ethical approval for the study was obtained from Institutional Review committee approval was obtained, and written informed consent was secured from all participants prior to enrolment.\u003c/p\u003e \u003cp\u003eConsecutive patients undergoing primary vitreoretinal surgery were enrolled by purposive sampling. Inclusion criteria included patients over 18years to be scheduled for primary vitreoretinal surgery at BPKLCOS. Exclusion criteria comprised of pre-existing glaucoma or ocular hypertension, neovascular glaucoma, active uveitis, penetrating or open globe injury, blunt ocular trauma with documented angle damage, previous vitreoretinal surgery in the study eye and intraocular infection. A total of 46 eyes of 42 patients met these criteria and completed the study protocol.\u003c/p\u003e \u003cp\u003eAll procedures were performed by experienced vitreoretinal surgeons using 20-gauge or small-gauge (23G/25G) PPV systems. Tamponade selection of C3F8 gas, silicon oil (SOI), air, or Band Buckle combined with silicon oil (BB\u0026thinsp;+\u0026thinsp;SOI) was made at the operating surgeon's discretion based on the primary diagnosis and intraoperative findings. Intraoperative endolaser photocoagulation was applied when clinically indicated.\u003c/p\u003e \u003cp\u003eThe primary outcome was IOP measured by Goldmann applanation tonometry (GAT) at four time points: pre-operatively (baseline), and on POD1, POD7, and POD30. Secondary outcomes were anterior chamber angle (ACA) and anterior chamber depth (ACD), both assessed using the Sirius Scheimpflug-Placido topographer (Costruzione Strumenti Oftalmici, Italy) at baseline and POD30.\u003c/p\u003e \u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStatistical Analysis\u003c/h2\u003e \u003cp\u003eData were analysed using SPSS v23. Normality was assessed by Kolmogorov-Smirnov and Shapiro-Wilk tests. IOP and ACD were non-normally distributed and analysed with the Friedman test (overall group comparison) and Wilcoxon signed-rank test (pairwise post-hoc). ACA was normally distributed and analysed with paired t-test and one-way ANOVA. Statistical significance was set at p\u0026thinsp;\u0026lt;\u0026thinsp;0.05.\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003eDemographic and Clinical Characteristics\u003c/h2\u003e \u003cp\u003eOf 102 vitreoretinal procedures performed during the study period, 46 eyes of 42 patients fulfilled inclusion criteria. Mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD age was 52.61\u0026thinsp;\u0026plusmn;\u0026thinsp;17.23 years (range 19\u0026ndash;78 years); 39.13% of eyes were from patients in the 61\u0026ndash;80 year age, and 36.95% from patients aged 41\u0026ndash;60 years. The cohort was male-predominant (30 eyes, 65.21%; male-to-female ratio 1.8:1). Among systemic comorbidities, hypertension was present in 19.6%, diabetes mellitus in 17.4%, and both in 15.2% of cases, yielding a combined systemic vascular comorbidity burden of 52.2%.\u003c/p\u003e \u003cp\u003eThe most common retinal diagnoses were vitreous haemorrhage (VH) and rhegmatogenous retinal detachment (RRD), each accounting for 19.56% (n\u0026thinsp;=\u0026thinsp;9) of eyes, followed by proliferative diabetic retinopathy (PDR, 17.39%, n\u0026thinsp;=\u0026thinsp;8), and branch retinal vein occlusion (BRVO, 13.04%, n\u0026thinsp;=\u0026thinsp;6). Pars plan vitrectomy with Silicon oil insertion (SOI) was the most frequently used tamponade (43.47%, n\u0026thinsp;=\u0026thinsp;20), followed by C3F8 (30.43%, n\u0026thinsp;=\u0026thinsp;14), BB\u0026thinsp;+\u0026thinsp;SOI (15.21%, n\u0026thinsp;=\u0026thinsp;7), and air (10.86%, n\u0026thinsp;=\u0026thinsp;5). Intraoperative endolaser was performed in 60.87% of eyes (n\u0026thinsp;=\u0026thinsp;28).\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eIOP by Tamponade Group\u003c/h3\u003e\n\u003cp\u003eAfter Pars plana vitrectomy, internal tamponade was done using various substances like Silicon oil, expending gases like C3F8, air and external tamponade was done using belt and buckle.\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\u003eIOP dynamics stratified by tamponade group\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTamponade\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003en (%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eFriedman χ\u0026sup2;\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eOverall\u003c/p\u003e \u003cp\u003ep value\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003ePOD1 vs Pre-op\u003c/p\u003e \u003cp\u003ep value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSilicon Oil (SOI)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e20 (43.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e5.19\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.159\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.247\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eC3F8 Gas\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e14 (30.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e5.41\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.144\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.169\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAir\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e5 (10.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e8.25\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.051\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.680\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBand Buckle\u0026thinsp;+\u0026thinsp;SOI (BB\u0026thinsp;+\u0026thinsp;SOI)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e7 (15.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e9.49\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e0.023\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e0.018\u003c/b\u003e\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 \u003cem\u003e(Friedman test and Wilcoxon post-hoc)* Statistically significant (p\u0026thinsp;\u0026lt;\u0026thinsp;0.05).\u003c/em\u003e \u003c/p\u003e \u003cp\u003eOnly the BB\u0026thinsp;+\u0026thinsp;SOI group demonstrated a statistically significant overall IOP variation across the four time points (Friedman χ\u0026sup2; = 9.49; p value 0.023). Within this group, POD1 IOP was significantly higher than the pre-operative baseline (Wilcoxon p value 0.018), and a significant decline from POD1 to POD30 was confirmed (p value 0.046). No other tamponade group achieved overall statistical significance SOI (p value 0.159), C3F8 (p value 0.144), and air (p value 0.051) as shown in Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e.\u003c/p\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eIOP by Primary Retinal Diagnosis\u003c/h2\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eIOP dynamics stratified by primary retinal diagnosis (Friedman test with Wilcoxon post-hoc)\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" 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 \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDiagnosis\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003en (%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eχ\u0026sup2;\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eOverall\u003c/p\u003e \u003cp\u003eP value\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003ePOD1 vs Pre-op\u003c/p\u003e \u003cp\u003eP value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVitreous Hemorrhage (VH)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e9 (19.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.08\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.783\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.888\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRhegmatogenous RD (RRD)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e9 (19.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e11.63\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e0.009\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e0.007\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eProliferative DR (PDR)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e8 (17.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6.80\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.078\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.042\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBranch RVO (BRVO)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e6 (13.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4.50\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.212\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.684\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCentral RVO (CRVO)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e3 (6.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8.25\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.051\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.102\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFTMH / Other\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e11 (23.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u0026mdash;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eNS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eNS\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 \u003cem\u003e* Statistically significant (p\u0026thinsp;\u0026lt;\u0026thinsp;0.05). RD\u0026thinsp;=\u0026thinsp;retinal detachment; PDR\u0026thinsp;=\u0026thinsp;proliferative diabetic retinopathy; RVO\u0026thinsp;=\u0026thinsp;retinal vein occlusion; FTMH\u0026thinsp;=\u0026thinsp;full-thickness macular hole; NS\u0026thinsp;=\u0026thinsp;not significant.\u003c/em\u003e \u003c/p\u003e \u003cp\u003eAmong diagnostic subgroups, only the RRD group demonstrated a statistically significant overall IOP variation (Friedman χ\u0026sup2; = 11.625; p value 0.009). Post-hoc Wilcoxon analysis confirmed a significant rise on POD1 versus baseline (Z\u0026thinsp;=\u0026thinsp;\u0026minus;\u0026thinsp;2.675; p value 0.007), on POD7 versus POD1 (p value 0.028), and on POD30 versus POD1 (p value 0.035), indicating a sustained period of IOP elevation in RRD eyes extending beyond the first post-operative day. A trend toward IOP elevation on POD1 was observed in the PDR group (p value0.042) that did not achieve overall Friedman significance (p value 0.078) as shown in Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eEndolaser and IOP\u003c/h3\u003e\n\u003cp\u003eIn eyes that received intraoperative endolaser photocoagulation (n\u0026thinsp;=\u0026thinsp;28), the overall Friedman test revealed a statistically significant IOP variation across the four time points (χ\u0026sup2; = 11.543; p value 0.009). In contrast, no significant variation was observed in eyes that did not receive endolaser (n\u0026thinsp;=\u0026thinsp;18; Friedman p value 0.280), identifying intraoperative laser photocoagulation as an independent contributor to post-operative IOP elevation.\u003c/p\u003e\n\u003ch3\u003eAnterior Chamber changes\u003c/h3\u003e\n\u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab4\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eAnterior chamber angle and depth: pre-operative versus post-operative Day 30\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eParameter\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePre-operative\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003ePost-operative (Day 30)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003ep value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAC Angle (mean \u0026deg; \u0026plusmn; SD)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e34.02\u0026thinsp;\u0026plusmn;\u0026thinsp;7.36\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e35.28\u0026thinsp;\u0026plusmn;\u0026thinsp;7.42\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.363 (NS)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAC Depth (median mm\u0026thinsp;\u0026plusmn;\u0026thinsp;SD)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e3.24\u0026thinsp;\u0026plusmn;\u0026thinsp;0.52\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e3.41\u0026thinsp;\u0026plusmn;\u0026thinsp;0.60\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e0.020*\u003c/b\u003e\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 \u003cem\u003e* Wilcoxon signed-rank test (ACD). Paired t-test (ACA). NS\u0026thinsp;=\u0026thinsp;not significant; SD\u0026thinsp;=\u0026thinsp;standard deviation.\u003c/em\u003e \u003c/p\u003e \u003cp\u003eThe AC angle did not change significantly between baseline and POD30 (mean increase 1.26\u0026thinsp;\u0026plusmn;\u0026thinsp;9.30\u0026deg;; paired t-test p value 0.363). One-way ANOVA confirmed no significant difference in AC angle across tamponade subgroups at either baseline (p value 0.560) or POD30 (p value 0.353). In contrast, ACD increased significantly from a median of 3.24\u0026thinsp;\u0026plusmn;\u0026thinsp;0.52 mm pre-operatively to 3.41\u0026thinsp;\u0026plusmn;\u0026thinsp;0.60 mm at POD30 (Wilcoxon p value 0.020), corresponding to a mean increase of 0.19\u0026thinsp;\u0026plusmn;\u0026thinsp;0.59 mm. No significant ACD change was observed within any individual tamponade subgroup (all p\u0026thinsp;\u0026gt;\u0026thinsp;0.05) as shown in Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThis prospective observational study provides structured longitudinal data on IOP dynamics and anterior chamber changes following vitreoretinal surgery in a South Asian tertiary care context, enrolling 46 eyes across a one-year period. The central findings is a significant POD1 IOP peak, greatest in the BB\u0026thinsp;+\u0026thinsp;SOI and RRD subgroups, and independently associated with endolaser application\u0026mdash;are broadly consistent with the global literature, while the anterior segment morphometric data offer mechanistic insight that informs clinical management.\u003c/p\u003e \u003cp\u003eThe pattern of IOP elevation, peaking on POD1 and resolving to sub-baseline levels by POD30, mirrors findings reported by Framme et al[\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. (mean IOP 19.7\u0026thinsp;\u0026plusmn;\u0026thinsp;8.0 mmHg at 24 hours post-20G PPV) and Desai et al[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. (majority of elevations occurring within the first post-operative day). Multiple overlapping mechanisms operate in this acute window: inflammatory trabeculitis impairs trabecular outflow within hours of surgical manipulation; fibrinous anterior chamber reaction can produce pupillary membrane and secondary angle obstruction; choroidal congestion from endolaser or vortex vein compression causes forward rotation of the lens-iris diaphragm; and expanding gas tamponade volumetrically compresses the angle. By POD7, resolution of acute inflammation\u0026mdash;aided by topical corticosteroid therapy\u0026mdash;and partial gas resorption collectively restore outflow facility. The sub-baseline IOP observed at POD30 likely reflects the well-described long-term IOP-lowering effect of vitrectomy, postulated to result from improved posterior segment convection, enhanced uveoscleral outflow following vitreous removal, or subtle reduction in ciliary body secretory activity[\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe exclusive statistical significance of the BB\u0026thinsp;+\u0026thinsp;SOI group among tamponade subgroups (overall p value 0.023) is mechanistically coherent. The encircling scleral band compresses the vortex veins, impairing choroidal venous drainage and triggering ciliary body engorgement and anterior rotation, thereby narrowing or closing the trabecular angle. Silicon oil adds a second independent mechanism: in aphakic or pseudophakic eyes with a disrupted posterior capsule, oil may migrate anteriorly to block the pupil or angle directly, while emulsified oil droplets and oil-laden macrophages obstruct the trabecular meshwork over time[\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. The absence of significant IOP elevation in the SOI-alone, C3F8, and air groups contrasts with findings from Xu et al[\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. and Framme et al[\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e], and is most likely attributable to the small intra-subgroup sample sizes limiting statistical power, combined with the expertise-related reduction in gas overfill and careful oil volume calibration by experienced surgeons at BPKLCOS.\u003c/p\u003e \u003cp\u003eThe persistent and significant IOP elevation in the RRD subgroup across POD1 through POD30 (p value 0.007, 0.028, and 0.035, respectively) reflects the complexity of RRD management at this centre: all RRD cases received silicon oil, the majority underwent endolaser, and a proportion required scleral buckling\u0026mdash;thus concentrating multiple risk factors within this diagnostic category. The underlying pathophysiology is further compounded by the marked inflammatory response to longstanding retinal detachment, characterised by elevated aqueous flare, breakdown of the blood-retinal barrier, and trabecular obstruction by dispersed retinal pigment epithelial cells and inflammatory debris[\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. Pillai et al[\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e] similarly identified RD as the diagnostic category with the highest risk of post-operative IOP elevation (49.2% of eyes), while Kovacic et al[\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. confirmed retinal detachment as an independent predictor of greater IOP increase following PPV.\u003c/p\u003e \u003cp\u003eEndolaser photocoagulation was identified as an independent risk factor in the present study (Friedman p\u0026thinsp;=\u0026thinsp;0.009 in laser-treated versus p\u0026thinsp;=\u0026thinsp;0.280 in untreated eyes). Laser-induced prostaglandin release stimulates uveoscleral outflow reduction, while choroidal oedema secondary to photocoagulation causes anterior displacement of the lens-iris diaphragm. These mechanisms are well-characterised in the laser literature and have direct implications for perioperative management: consideration should be given to prophylactic topical carbonic anhydrase inhibitors or beta-blockers at the conclusion of procedures involving extensive endolaser.\u003c/p\u003e \u003cp\u003eThe absence of a significant change in AC angle at POD30 (p\u0026thinsp;=\u0026thinsp;0.363), coupled with the lack of tamponade-specific angle differences, strongly supports the predominance of open-angle mechanisms in this cohort\u0026mdash;consistent with the conclusions of Chang[\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e] and Mansukhani et al[\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e] both of whom identified open-angle glaucoma, rather than angle-closure, as the characteristic long-term glaucomatous complication of vitreoretinal surgery. This mechanistic insight favours the use of aqueous suppressants over miotics for acute IOP management in the post-vitrectomy setting.\u003c/p\u003e \u003cp\u003eThe significant increase in ACD at POD30 (+\u0026thinsp;0.19 mm; p\u0026thinsp;=\u0026thinsp;0.020) is an apparently paradoxical finding in a setting where forward displacement of the lens-iris diaphragm by tamponade agents might be expected to shallow the anterior chamber. This observation is likely explained by the one-month interval of the measurement: by POD30, gas has largely resorbed (SF6 within 10\u0026ndash;14 days; C3F8 by 6\u0026ndash;8 weeks), choroidal congestion has resolved, and the posterior vitreous traction that previously displaced the lens anteriorly has been relieved by the vitrectomy itself. A comparison of immediate post-operative ACD (not measured in this study) with the POD30 value would be needed to determine whether an initial shallowing\u0026mdash;as documented by Neudorfer et al[\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e] preceded the deepening observed at one month.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003ePost-vitrectomy IOP elevation is a predominantly early phenomenon that peaks on POD1 and resolves to sub-baseline values by one month in the majority of patients. The BB\u0026thinsp;+\u0026thinsp;SOI tamponade combination, RRD as the underlying diagnosis, and intraoperative endolaser photocoagulation each independently increase the risk of significant post-operative IOP elevation. The open-angle mechanism predominates, as evidenced by the absence of significant post-operative change in the anterior chamber angle. These findings support the implementation of structured, risk-stratified IOP monitoring protocols in vitreoretinal surgical programmes, with targeted prophylactic anti-glaucoma therapy in high-risk subgroups to prevent potentially irreversible glaucomatous sequelae.\u003c/p\u003e \u003cdiv id=\"Sec13\" class=\"Section2\"\u003e \u003ch2\u003eLimitation\u003c/h2\u003e \u003cp\u003eThe relatively small sample size limits statistical power for subgroup analyses and precludes robust multivariate modeling of independent risk factors. The short follow-up period (30 days) does not capture delayed-onset glaucoma, particularly in silicone oil\u0026ndash;filled eyes. Additionally, variability in surgical technique and tamponade selection introduces potential confounding. Future studies with larger cohorts, longer follow-up, and multivariate regression analysis are warranted.\u003c/p\u003e \u003c/div\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eACA: Anterior chamber angle\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eACD: Anterior Chamber depth\u003c/p\u003e\n\u003cp\u003eBB: Band Buckle\u003c/p\u003e\n\u003cp\u003eBRVO: Branch retinal vein occlusion\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eCRVO: central retinal vein occlusion\u003c/p\u003e\n\u003cp\u003eFTMH: full thickness macular hole\u003c/p\u003e\n\u003cp\u003eIOP: Intra ocular pressure\u003c/p\u003e\n\u003cp\u003ePOD: Post-operative day\u003c/p\u003e\n\u003cp\u003ePDR: Proliferative Diabetic retinopathy\u003c/p\u003e\n\u003cp\u003eRRD: Rhegmatogenous retinal detachment\u003c/p\u003e\n\u003cp\u003eSOI: Silicon Oil\u003c/p\u003e\n\u003cp\u003eVitreous Haemorrhage (VH)\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthical approval\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWas obtained from the ethics committee of \u003cstrong\u003eInstitutional Review Committee of Institute of Medicine\u003c/strong\u003e, \u003cstrong\u003eTribhuvan University\u003c/strong\u003e, Kathmandu, Nepal with the Reference number of 341(6-11) E2 in accordance with the Declaration of Helsinki.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eHuman ethics/ Consent to Participate:\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors certify that INFORMED CONSENT were obtained from all the patients who participated in the study.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication:\u0026nbsp;\u003c/strong\u003eThis is not applicable here.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData availability:\u0026nbsp;\u003c/strong\u003eThe data used to support the findings of this study are available from the corresponding author upon a request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements:\u0026nbsp;\u003c/strong\u003e Not applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests:\u0026nbsp;\u003c/strong\u003eThere is not competing interest in publication of this research.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding:\u0026nbsp;\u003c/strong\u003eThere is not funding received for this study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026apos; contributions:\u003c/strong\u003e PA and PK collected data. 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Med Hypothesis Discov Innov Ophthalmol. 2017;6(3):76\u0026ndash;81. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.51329/mehdiophthal176\u003c/span\u003e\u003cspan address=\"10.51329/mehdiophthal176\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-ophthalmology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"boph","sideBox":"Learn more about [BMC Ophthalmology](http://bmcophthalmol.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/boph","title":"BMC Ophthalmology","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Anterior chamber, Endolaser, Intraocular pressure, Pars plana vitrectomy Rhegmatogenous retinal detachment, Scleral buckle, Silicone oil","lastPublishedDoi":"10.21203/rs.3.rs-9509509/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-9509509/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eIncrease in IOP after Vitreoretinal surgery is uncommon but sight threatening complication. This study aims to determine the incidence and risk factors of intraocular pressure (IOP) elevation following vitreoretinal surgery.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eA prospective, hospital-based observational cohort study was conducted at BPKLCOS, Kathmandu, Nepal (February 2019 \u0026ndash; February 2020). Forty-six eyes of 42 patients undergoing primary vitreoretinal surgery were enrolled. IOP was measured by Goldmann applanation tonometry pre-operatively and on post-operative days 1, 7, and 30 (POD1, POD7, POD30). Anterior chamber angle (ACA) and depth (ACD) were quantified using the Sirius Scheimpflug-Placido topographer at baseline and POD30. Statistical analysis employed the Friedman test and Wilcoxon signed-rank test for non-normal data (IOP, ACD) and paired t-test with one-way ANOVA for normally distributed data (ACA).\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eMean age of the study population was 52.61\u0026thinsp;\u0026plusmn;\u0026thinsp;17.23 years; male-to-female ratio 1.8:1. IOP rose significantly on POD1 (median 17 vs. 15 mmHg; p\u0026thinsp;=\u0026thinsp;0.006) and declined by POD30 (median 13 mmHg; p value 0.001 vs. POD1). The Band Buckle\u0026thinsp;+\u0026thinsp;Silicon Oil (BB\u0026thinsp;+\u0026thinsp;SOI) group showed the greatest IOP elevation (overall p value 0.023; POD1 p value 0.018). Rhegmatogenous retinal detachment (RRD) was the diagnosis most significantly associated with sustained IOP elevation (overall p value 0.009; POD1 p value 0.007). Intraoperative endolaser was independently associated with IOP rise (p\u0026thinsp;=\u0026thinsp;0.009). Male patients showed statistically significant overall IOP elevation (Friedman χ\u0026sup2; = 11.885; p value 0.008). ACA did not change significantly (p value 0.363), ACD increased significantly at POD30 (mean\u0026thinsp;+\u0026thinsp;0.19 mm; p value 0.020).\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003ePost-vitrectomy IOP elevation peaks on POD1 and gradually decreases over the time. This is most pronounced in eyes undergoing RRD repair with BB\u0026thinsp;+\u0026thinsp;SOI and those receiving intraoperative endolaser. Although ACA does not change but ACD deepened which was statistically significant.\u003c/p\u003e","manuscriptTitle":"Intraocular Pressure Elevation Following Vitreoretinal Surgery - A Prospective Cohort Study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-05-11 10:51:07","doi":"10.21203/rs.3.rs-9509509/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"editorInvitedReview","content":"","date":"2026-05-03T14:36:00+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-05-03T07:06:31+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"202240398920407947220497616215087075352","date":"2026-05-03T05:56:13+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"93164829886247621638259641544274445733","date":"2026-05-01T15:34:47+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"247430511448391769458229849109114727369","date":"2026-05-01T14:47:48+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2026-05-01T05:36:22+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2026-04-27T08:16:40+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2026-04-27T03:31:38+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2026-04-27T03:31:02+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Ophthalmology","date":"2026-04-23T17:32:32+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-ophthalmology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"boph","sideBox":"Learn more about [BMC Ophthalmology](http://bmcophthalmol.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/boph","title":"BMC Ophthalmology","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"f065d6f3-b4dc-464d-bf88-a0d5c50ba8b4","owner":[],"postedDate":"May 11th, 2026","published":true,"recentEditorialEvents":[{"type":"editorInvitedReview","content":"","date":"2026-05-03T14:36:00+00:00","index":56,"fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-05-03T07:06:31+00:00","index":53,"fulltext":""},{"type":"reviewerAgreed","content":"202240398920407947220497616215087075352","date":"2026-05-03T05:56:13+00:00","index":51,"fulltext":""},{"type":"reviewerAgreed","content":"93164829886247621638259641544274445733","date":"2026-05-01T15:34:47+00:00","index":48,"fulltext":""},{"type":"reviewerAgreed","content":"247430511448391769458229849109114727369","date":"2026-05-01T14:47:48+00:00","index":46,"fulltext":""},{"type":"reviewersInvited","content":"22","date":"2026-05-01T05:36:22+00:00","index":"","fulltext":""}],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2026-05-11T10:51:08+00:00","versionOfRecord":[],"versionCreatedAt":"2026-05-11 10:51:07","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-9509509","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-9509509","identity":"rs-9509509","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}