Effect of combined mature cataract surgery and intravitreal ranibizumab injection in eyes with pre-existing diabetic macular edema

Effect of combined mature cataract surgery and intravitreal ranibizumab injection in eyes with pre-existing diabetic macular edema | 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 Effect of combined mature cataract surgery and intravitreal ranibizumab injection in eyes with pre-existing diabetic macular edema Yao Shen, Xi Zhu, Aiqiu Li, Min Ji, Huaijin Guan This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6171645/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 11 Aug, 2025 Read the published version in BMC Ophthalmology → Version 1 posted 7 You are reading this latest preprint version Abstract Purpose: This study aimed to compare the functional and anatomical outcomes of combined cataract surgery and intravitreal ranibizumab injection in eyes with pre-existing diabetic macular edema (DME) and preoperatively obscured fundus due to advanced cataracts. Methods: After screening 350 eyes with diabetic cataracts and preoperatively obscured fundus, 39 eyes with intraoperatively confirmed DME were included in the final analysis. Eyes were randomly assigned to either the ranibizumab group (20 eyes) or the delayed treatment group (19 eyes). Best-corrected visual acuity (BCVA), total macular volume (TMV), and central subfield thickness (CST) were evaluated at 1, 4, and 12 weeks postoperatively. Intraoperative retinal examination techniques, including 25G optical fiber, wide-angle retinal photography, and intraoperative OCT, were used to enable real-time diagnosis and intervention. Results: At 12 weeks, the ranibizumab group showed a mean BCVA improvement of 34 letters, compared to 23 letters in the delayed group (P=0.03). The mean change in CST was -68 μm in the ranibizumab group and 33 μm in the delayed group (P=0.05). Changes in TMV were similar between the two groups at 12 weeks. Conclusion: Intravitreal ranibizumab injection during cataract surgery significantly improved visual acuity and reduced central subfield thickness at 12 weeks postoperatively in patients with pre-existing DME and preoperatively obscured fundus. This study highlights the importance of intraoperative retinal examination and timely anti-VEGF intervention in improving visual outcomes for this challenging patient population. cataract diabetic macular edema ranibizumab intraoperative fundus examination Figures Figure 1 Figure 2 Figure 3 Figure 4 Short Summary This study demonstrates that timely diagnosis and treatment of diabetic macular edema (DME) during cataract surgery significantly improves short-term postoperative visual outcomes. 1 Introduction The global prevalence of diabetes, longer life expectancies, and an aging population are expected to significantly increase cataract surgery rates among diabetic patients [ 1 ] . Diabetics face a higher risk of postoperative complications, particularly in the presence of unstable hyperglycemia, reduced corneal endothelial cell counts, diabetic retinopathy (DR), or diabetic macular edema (DME) [ 2 ] . Approximately 10% of diabetic patients develop DME, and when combined with cataracts, vision loss can severely impact daily life [ 3 ] . Currently, there are no specific guidelines for managing DME during cataract surgery. While surgical intervention effectively treats diabetic cataracts, performing surgery without addressing DME may accelerate retinal disease progression, compromising postoperative vision. Conversely, delaying cataract surgery to treat DME first can hinder retinal monitoring and increase surgical complexity as the cataract worsens. Thus, managing diabetic cataracts with concurrent retinal disease remains a significant challenge for ophthalmologists. A unique aspect of our study is the focus on patients with preoperatively obscured fundus due to advanced cataracts, a population often excluded from prior research due to the inability to perform high-quality preoperative retinal imaging. In these patients, traditional preoperative fundus examination is often impossible, leading to delayed diagnosis and treatment of DME. This delay can result in irreversible ocular complications and suboptimal visual outcomes [ 4 ] . To address this critical gap, we have developed an innovative approach that combines cataract surgery with real-time intraoperative retinal examination techniques, enabling immediate diagnosis and intervention for DME during the surgical procedure [ 5 ] . During the perioperative period, several treatment options are available for DME, including intravitreal anti-VEGF agents, steroids, and laser photocoagulation. Anti-VEGF therapy, supported by extensive literature, has revolutionized DME management globally [ 5 ] . Recent studies have highlighted the protective and beneficial effects of intravitreal injections administered during cataract surgery [ 4 ] . Previous studies have demonstrated that intravitreal ranibizumab injection immediately after cataract surgery or within the first postoperative week can effectively prevent or treat diabetic macular edema (DME) in patients with diabetic retinopathy [ 6 – 8 ] . Unlike previous studies, our research innovatively combined three intraoperative retinal examination techniques, enabling real preoperatively obscured fundus-time observation and evaluation of retinal conditions during cataract surgery, particularly in patients with obscured fundi [ 6 ] . This approach is particularly valuable for patients with advanced cataracts, where traditional preoperative fundus examination is often impossible . The present study aims to evaluate the functional and anatomical outcomes of combined cataract surgery and intravitreal anti-VEGF injection in eyes with pre-existing DME and preoperatively obscured fundus. By focusing on this specific patient population, our research addresses a critical gap in clinical practice, offering a novel strategy for timely diagnosis and intervention during cataract surgery. 2 Materials and Methods 2.1 Patients A total of 350 eyes with diabetic cataracts and preoperatively obscured fundus were screened for this study. Among these, 48 eyes were identified with diabetic macular edema (DME) during intraoperative examination. After excluding 9 eyes lost to follow-up, 39 eyes meeting the inclusion/exclusion criteria were included in the final analysis. The detection rate of DME in patients with preoperatively obscured fundus was 13.7% (48/350). This prospective randomized study included consecutive patients who underwent combined cataract surgery and intravitreal treatment at our institution between January 2021 and January 2022. The study adhered to institutional and governmental ethical guidelines and was conducted in accordance with the Declaration of Helsinki (1964) and its later amendments. Ethical approval was obtained from the Institutional Ethics Committee of the Affiliated Hospital of Nantong University, and all participants provided written informed consent using a form specifically designed and approved by the Eye Institute for prospective studies. Patients were eligible if they had a preoperative diagnosis of diabetic cataract with poor fundus visualization, intraoperative evidence of diabetic macular edema (DME), or moderate-to-severe diabetic retinopathy (DR). Exclusion criteria included intravitreal injection within the preceding 5 months, concurrent retinal diseases (e.g., active PDR level with new vessels in the disc and retina or vitreous hemorrhageretinal vein occlusion, retinal dystrophies, or age-related macular degeneration), glaucoma, or previous vitrectomy. Participants were informed that they would be randomly assigned to one of two groups using a random number table. For the 7 patients with bilateral involvement, the second eye was enrolled only after the first eye completed the 12-week follow-up, and treatment allocation (ranibizumab/delayed) was randomized independently for each eye to minimize intra-patient correlation. Patients in the delayed treatment group were informed during the first postoperative week that they would receive intravitreal injections for DME management. Based on previous studies demonstrating the efficacy of intravitreal ranibizumab injection immediately after cataract surgery or within the first postoperative week, and considering that our patients had advanced cataracts with preoperatively obscured fundus, significant phacoemulsification energy usage during surgery, and a higher likelihood of postoperative corneal edema, we chose to administer treatment for macular edema at 4 weeks postoperatively in the delayed group and completed follow-up assessments [ 6 – 8 ] . Our delayed treatment group intentionally included both protocol-driven and financially constrained subgroups to reflect real-world practice challenges. 2.2 Preoperative Evaluation and Follow-Up Prior to cataract surgery, all patients underwent comprehensive ophthalmic evaluations, including slit-lamp examination, dilated fundus examination, non-contact tonometry for intraocular pressure (IOP), fundus B-scan ultrasonography and optical coherence tomography (OCT). Preoperative OCT was attempted but deemed unreliable due to media opacity; definitive imaging was obtained. Visual acuity was assessed using the Early Treatment Diabetic Retinopathy Study (ETDRS) scale, and diabetic retinopathy (DR) severity was graded according to the Diabetic Retinopathy Study (DRS) criteria. Postoperative follow-up examinations were conducted at 1 week, 1 month, and 3 months, with each visit including a complete ophthalmologic evaluation. 2.3 Surgical Technique All surgeries were performed by three experienced surgeons using a standardized technique under topical anesthesia. A 2.4-mm temporal clear corneal incision was made, followed by continuous curvilinear capsulorhexis. After hydrodissection, phacoemulsification of the nucleus and cortical aspiration were performed. Prior to intraocular lens (IOL) implantation, the fundus was examined using multiple approaches [ 4 ] , and patients in the intervention group were randomized based on the findings. In the intervention group, a distance gauge was used to mark a point 4 mm from the corneoscleral rim in the inferotemporal quadrant. A needle was inserted vertically at the mark, and ranibizumab was slowly injected into the vitreous cavity. The needle was then withdrawn, and the injection site was moistened with sodium lactate Ringer's solution and gently compressed with a swab. Tobramycin-dexamethasone ophthalmic ointment was applied to the conjunctival sac, and the eye was covered with gauze before the patient was transferred to the ward. 2.4 Postoperative Medication: All patients received the same postoperative medication regimen: topical fluoroquinolone four times daily for one week, topical dexamethasone four times daily for one week (tapered over the following two weeks), and a topical nonsteroidal anti-inflammatory drug for three weeks. 2.5 Intraoperative Retinal Examination: Following routine surface anesthesia, a limbal incision was made, and continuous curvilinear capsulorhexis was performed. The lens was separated using irrigation, followed by phacoemulsification and cortical aspiration. Each imaging modality added approximately 3–5 minutes to surgery time, with no reported patient discomfort under topical anesthesia. 2.5.1 25G Optical Fiber with Corneal Contact Lens: After removing the opaque crystalline lens and aspirating residual cortex, viscoelastic was injected into the anterior chamber. A sterile 25G optical fiber was inserted through the main corneal incision (Fig. 1 A), and a corneal contact lens (11D flat-concave) coated with viscoelastic was placed on the cornea. The microscope light was turned off, and the focus was adjusted to visualize the posterior pole. Surgical forceps were used to gently manipulate the eye for peripheral retinal observation. Findings were photographed and recorded (Fig. 2 ). 2.5.2 SW-8000 Wide-Angle Probe Camera: After removing the optical fiber and washing away residual viscoelastic, a sterile SW-8000 probe camera (SW-8000, Tianjin Suowei Electronic Technology Co.,Ltd) was positioned vertically above the cornea (Fig. 1 B). The optic disc, macula, and retinal quadrants (temporal, superior, nasal, and inferior) were sequentially examined on the screen, and images were captured for documentation (Fig. 3 ). 2.5.3 iVue OCT ( Optovue, Inc., Fremont, CA, USA ): Following IOL implantation, the iOCT was used to evaluate the macular layers (Fig. 1 C). Images were captured and recorded for analysis (Fig. 4 ). Based on intraoperative retinal examination findings, eligible patients were randomized into groups. For those requiring pharmacological intervention, intravitreal ranibizumab injection was administered after obtaining informed consent and completing cataract surgery. 2.6 Statistical Analysis Numerical data were summarized as means ± standard deviation (SD) if normally distributed, or as medians with interquartile ranges (IQR) if non-normally distributed. Categorical data were presented as frequencies and percentages. Normality of data distribution was assessed using the Shapiro-Wilk test. For non-normally distributed numerical variables, between-group comparisons were performed using the Mann-Whitney U test or Kruskal-Wallis test, as appropriate. Within-group comparisons for non-normally distributed variables were analyzed using the Friedman test for repeated measures. Categorical data were compared using the chi-square test or Fisher’s exact test, depending on the sample size. All statistical tests were two-sided, and a P value < 0.05 was considered statistically significant. Missing data were addressed using multiple imputation methods, assuming data were missing at random (MAR). Sensitivity analyses were conducted to evaluate the impact of missing data on the results. For variables with more than 10% missing values, complete case analysis was performed to ensure robustness of the findings. Statistical analyses were conducted using SPSS version 25.0 (IBM Corp., Armonk, NY, USA) and R software (version 4.0.3, R Foundation for Statistical Computing, Vienna, Austria). 3 Results A total of 65 eyes from 39 patients who underwent combined cataract surgery and intravitreal treatment were initially enrolled. Of these, 10 eyes were excluded for not meeting inclusion criteria, 6 were lost to follow-up, and 10 were withdrawn upon request. Ultimately, 39 eyes meeting the inclusion/exclusion criteria were included in the final analysis. All 65 eyes underwent successful surgery without intraoperative or postoperative complications. Intravitreal treatment was administered as a standard injection at the conclusion of surgery, with 20 eyes receiving ranibizumab and 19 eyes assigned to the untreated group. A total of 350 eyes with diabetic cataracts and preoperatively obscured fundus were screened, of which 48 eyes (13.7%) were identified with diabetic macular edema (DME) during intraoperative examination. After excluding 9 eyes lost to follow-up, 39 eyes were included in the final analysis. As shown in Table 1 , the clinical characteristics of the 32 patients at screening demonstrated no significant differences between the two groups in terms of gender distribution, age, duration of diabetes, insulin use, history of panretinal photocoagulation (PRP), best-corrected visual acuity (BCVA), intraocular pressure (IOP), central subfield thickness (CST), or total macular volume (TMV). Table 2 summarizes the BCVA, CST, and TMV values for the 32 patients at each follow-up time point (1 week, 4 weeks, and 12 weeks). Table 1 Baseline Patient Characteristics Characteristic Ranibizumab (N = 20) Delayed (N = 19) P Male: female 11:9 6:13 0.1 Age, years 62.2 ± 13.0 59.9 ± 10.3 0.6 Duration of diabetes, years 10.2 ± 4.5 10.3 ± 2.6 0.5 Insulin used, (%) 7(35) 7(37) 0.7 Hypertension, No. (%) 10(60) 9(47) 0.1 PRP history, (%) 5(25) 2(11) 1.0 BCVA, ETDRS letters 35.9 ± 15.7 37.8 ± 15.8 0.8 IOP, mmHg 16.2 ± 2.5 16.2 ± 2.4 0.9 CST, µm 343.2 ± 121.3 312.7 ± 107.5 0.6 TMV, mm 3 10.5 ± 1.9 10.5 ± 1.3 0.9 Table 2 Postoperative BCVA, CST, and TMV* BCVA CST TMV Ranibizumab Delayed Ranibizumab Delayed Ranibizumab Delayed 1 Week 65.4 ± 10.2 61.7 ± 15.8 283.2 ± 65.2 293.4 ± 86.5 11.0 ± 1.5 11.0 ± 1.1 4 weeks 69.2 ± 9.5 62.6 ± 18.5 295.5 ± 64.1 320.6 ± 113.8 11.0 ± 1.6 11.3 ± 1.2 12 weeks 70.6 ± 10.9 61.1 ± 16.4 275.0 ± 54.8 346.5 ± 108.7 11.2 ± 1.3 11.7 ± 1.2 *The units of BCVA, CST, and TMV are ETDRS letter numbers, µm, and mm 3 , respectively. 3.1. Change in BCVA, Relative to Baseline The two groups exhibited clinically significant differences in terms of the change of BCVA from baseline at 3-month follow-up visits (P = 0.04, Table 3 ). Table 3 Mean Changes in BCVA From Baseline Changes in BCVA From Baseline Ranibizumab Delayed P 1week 29.4 ± 16.4 23.9 ± 10.7 0.1 4 weeks 33.2 ± 15.8 24.8 ± 13.6 0.1 12 weeks 34.6 ± 15.3 23.3 ± 14.3 0.04* 3.2. Change in Central Subfield Thickness Relative to Baseline The two groups did not significantly differ in terms of the mean CST changes at 1-week, 4-week follow-up visits (P = 0.08 and 0.2, respectively, Table 4 ). However, there was a significant clinical difference between the two groups during 3-month follow-up (P = 0.05). Table 4 Mean Changes in CST From Baseline Changes in CST From Baseline Ranibizumab Delayed P 1week -60.0 ± 77.3 -19.3 ± 59.8 0.08 4 weeks -47.0 ± 99.7 7.95 ± 103.9 0.2 12 weeks -68.2 ± 116.7 33.8 ± 143.9 0.05* 3.3. Change in Total Macular Volume Relative to Baseline The trend of TMV changes in the two groups is similar, and no statistical significance was found after comparison (P = 0.8, 0.4, and 0.2, respectively, Table 5 ). Table 5 Mean Changes in TMV From Baseline Changes in CST From Baseline Ranibizumab Delayed P 1week 0.48 ± 1.4 0.50 ± 1.2 0.8 4 weeks 0.45 ± 1.9 0.73 ± 1.4 0.4 12 weeks 0.69 ± 1.4 1.1 ± 1.4 0.2 3.4. Safety of Ranibizumab Injection Considering adverse events, two occurred in the ranibizumab injection group. They were both associated with high postoperative IOP at one week. After timely intervention with ocular hypotensive therapy, there were no more serious complications in these patients. We did not systematically evaluate pseudophakic CME incidence due to challenges in differentiating postoperative inflammation-mediated edema from pre-existing DME progression. Future studies should employ FA or en face OCT to dissect these mechanisms. 4 Discussion The primary focus of this study was to evaluate the efficacy and safety of intravitreal anti-VEGF drug injection during cataract surgery in patients with pre-existing diabetic macular edema (DME). Our findings align with previous research indicating that cataract surgery in diabetic patients can exacerbate DME, primarily due to metabolic dysregulation, retinal microcirculation changes, and inflammatory responses [ 3 , 9 ] . However, unlike many studies that exclude patients with significant optical media opacities, our study specifically targeted patients with obscured fundi, utilizing innovative intraoperative retinal examination techniques to enable real-time diagnosis and intervention. This approach addresses a critical gap in clinical practice, as delayed DME detection and treatment can lead to irreversible ocular complications [ 6 ] . The rationale for intraoperative anti-VEGF injection stems from reports that cataract surgery alone may transiently worsen DME in diabetic patients due to inflammatory and metabolic perturbations [ 3 , 9 ] . Our study observed that combined surgery and ranibizumab therapy attenuated this effect, as evidenced by greater BCVA improvement and CST reduction compared to delayed treatment. However, our study diverges from some earlier findings in that changes in retinal thickness did not reach statistical significance, possibly due to the preoperative inability to accurately measure retinal thickness in patients with advanced cataracts [ 10 ] . This highlights the importance of intraoperative imaging techniques in guiding treatment decisions . Current DME management includes anti-VEGF therapy, corticosteroids, laser photocoagulation, and surgical interventions. While anti-VEGF agents have become the first-line treatment due to their efficacy in reducing vascular leakage and edema, their short duration of action and high cost remain limitations [ 11 – 13 ] . Corticosteroids, such as the sustained-release dexamethasone implant (Ozurdex®) and fluocinolone acetonide implant (Iluvien®), offer an alternative by providing prolonged anti-inflammatory effects with less frequent dosing [ 11 , 13 ] . These agents may be particularly beneficial in patients with chronic DME or those who cannot comply with frequent anti-VEGF injections. However, their use is often limited by the risk of intraocular pressure elevation and cataract progression [ 14 ] . Recent trials further highlight the role of sustained-release corticosteroids in stabilizing macular anatomy and reducing retreatment frequency [ 13 ] . Laser therapy, once the gold standard, has been largely supplanted by pharmacologic treatments but remains valuable in specific cases [ 15 ] . Our study supports the use of intravitreal anti-VEGF injections during cataract surgery as a viable strategy to improve visual outcomes and control DME progression [ 6 , 7 ] . The timing of intravitreal ranibizumab injection in the delayed group was set at 4 weeks postoperatively, based on previous studies demonstrating the efficacy of immediate or early postoperative anti-VEGF therapy [ 6 – 8 ] . Additionally, our patients had advanced cataracts with preoperatively obscured fundus, which required significant phacoemulsification energy during surgery, leading to a higher likelihood of postoperative corneal edema. Delaying treatment until 4 weeks postoperatively allowed for the resolution of early postoperative inflammation and corneal edema, ensuring more accurate assessment and treatment of macular edema. The 4-week delay in the control group was designed to balance two factors: (a) the need to resolve early postoperative inflammation and corneal edema for accurate DME assessment, and (b) minimizing potential harm from treatment delay. Existing evidence suggests that short-term delays (≤ 1 month) in initiating anti-VEGF therapy for DME do not preclude good long-term outcomes if subsequent treatment is consistent [ 6 , 16 ] . In our cohort, despite the delay, no eyes developed irreversible structural sequelae (e.g., ellipsoid zone disruption on OCT), though longer follow-up is needed to confirm this observation." This study has several limitations. First, the small sample size (39 eyes) may limit the generalizability of our findings. Future studies should expand the cohort to include a more diverse patient population and conduct subgroup analyses to identify specific patient profiles that benefit most from combined cataract surgery and anti-VEGF therapy. Second, the 12-week follow-up period is relatively short, and longer-term studies are needed to assess the durability of treatment effects and potential late complications [ 8 , 12 ] . Third, when accounting for intra-patient correlation using mixed-effects models, the statistical significance of some outcomes was attenuated ( P > 0.05), likely due to reduced power from the smaller effective sample size in this analysis. However, the preservation of effect sizes (e.g., consistent BCVA letter gains) suggests that the clinical relevance of combined therapy warrants further validation in larger cohorts with unilateral involvement. Finally, our study focused solely on ranibizumab; future research should compare the efficacy of different anti-VEGF agents, corticosteroids, and combination therapies to optimize treatment protocols [ 17 , 18 ] . Additionally, incorporating advanced imaging modalities such as optical coherence tomography angiography (OCTA) and inflammatory biomarker analysis could provide deeper insights into disease mechanisms and guide more personalized treatment approaches [ 19 , 20 ] . For example, staging DME based on OCT and OCTA findings may help tailor interventions to individual patient needs, while pre-operative testing of inflammatory factors could identify patients who would benefit from adjunctive anti-inflammatory therapy [ 20 , 21 ] . Future studies should explore these strategies to optimize treatment protocols and improve patient outcomes [ 12 ] . Declarations Data Availability The data that support the findings of this study are available from the corresponding author upon reasonable request. Ethical Approval This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the Ethics Committee of the Affiliated Hospital of Nantong University. The trial registration number is 2019-K068. Consent Informed consent was obtained from all participating subjects after they were given an explanation of the study. Conflicts of Interest The authors declare that they have no conflicts of interest. Acknowledgments I extend my heartfelt gratitude to all colleagues for their meticulous efforts and professional dedication during the fieldwork execution. Particular recognition is owed to my research supervisor, whose scholarly insights critically shaped the manuscript's analytical rigor. This dataset's enhanced validity fundamentally derives from our collaborative intellectual enterprise, wherein each contributor's expertise served as an indispensable epistemic pillar. Funding This work was supported by Nantong Municipal Science and Technology Project (No. MS22022020). Author Contribution Yao Shen and Xi Zhu wrote the main manuscript text and Aiqiu Li prepared figures. Min Ji and Huaijin Guan reviewed the manuscript. References Chan LKY, Lin SS, Chan F, et al. Optimizing treatment for diabetic macular edema during cataract surgery[J]. Front Endocrinol (Lausanne), 2023, 14: 1106706. Wang W, Lo ACY. Diabetic Retinopathy: Pathophysiology and Treatments[J]. Int J Mol Sci, 2018, 19(6). Patel JI, Hykin PG, Cree IA. Diabetic cataract removal: postoperative progression of maculopathy--growth factor and clinical analysis[J]. Br J Ophthalmol, 2006, 90(6): 697-701. Su Shu WS, Wu Jian, et al. Feasibility and clinical significance of intraoperative real-time fundus examination in cataractous eyes. In: Chin J Exp Ophthalmol, Vol. 04, 2020: 331-335. Su S, Wu J, Ji M, et al. [A comparative study of three intraoperative real-time fundus examinations in cataractous eyes][J]. Zhonghua Yan Ke Za Zhi, 2021, 57(11): 850-856. Udaondo P, Garcia-Pous M, Garcia-Delpech S, et al. Prophylaxis of macular edema with intravitreal ranibizumab in patients with diabetic retinopathy after cataract surgery: a pilot study[J]. J Ophthalmol, 2011, 2011: 159436. Zhao LQ, Cheng JW. A Systematic Review and Meta-Analysis of Clinical Outcomes of Intravitreal Anti-VEGF Agent Treatment Immediately after Cataract Surgery for Patients with Diabetic Retinopathy[J]. J Ophthalmol, 2019, 2019: 2648267. Starr MR, Mahr MA, Smith WM, et al. Outcomes of Patients With Active Diabetic Macular Edema at the Time of Cataract Surgery Managed With Intravitreal Anti-Vascular Endothelial Growth Factor Injections[J]. Am J Ophthalmol, 2021, 229: 194-199. Wu J, Zhong Y, Yue S, et al. Aqueous Humor Mediator and Cytokine Aberrations in Diabetic Retinopathy and Diabetic Macular Edema: A Systematic Review and Meta-Analysis[J]. Dis Markers, 2019, 2019: 6928524. Boyer DS, Yoon YH, Belfort R, Jr., et al. Three-year, randomized, sham-controlled trial of dexamethasone intravitreal implant in patients with diabetic macular edema[J]. Ophthalmology, 2014, 121(10): 1904-1914. Schmidt-Erfurth U, Garcia-Arumi J, Bandello F, et al. Guidelines for the Management of Diabetic Macular Edema by the European Society of Retina Specialists (EURETINA)[J]. Ophthalmologica, 2017, 237(4): 185-222. Brown DM, Emanuelli A, Bandello F, et al. KESTREL and KITE: 52-Week Results From Two Phase III Pivotal Trials of Brolucizumab for Diabetic Macular Edema[J]. Am J Ophthalmol, 2022, 238: 157-172. Wykoff CC, Garweg JG, Regillo C, et al. KESTREL and KITE Phase 3 Studies: 100-Week Results With Brolucizumab in Patients With Diabetic Macular Edema[J]. Am J Ophthalmol, 2024, 260: 70-83. Campochiaro PA, Marcus DM, Awh CC, et al. The Port Delivery System with Ranibizumab for Neovascular Age-Related Macular Degeneration: Results from the Randomized Phase 2 Ladder Clinical Trial[J]. Ophthalmology, 2019, 126(8): 1141-1154. Yang X, Cao Y, Cao X, et al. Anti-VEGF monotherapy versus anti-VEGF therapy combined with laser or intravitreal glucocorticoid therapy for diabetic macular edema: A Bayesian network meta-analysis[J]. Diabetes Obes Metab, 2025. Wells JA, Glassman AR, Ayala AR, et al. Aflibercept, Bevacizumab, or Ranibizumab for Diabetic Macular Edema: Two-Year Results from a Comparative Effectiveness Randomized Clinical Trial[J]. Ophthalmology, 2016, 123(6): 1351-1359. Rennie C, Lotery A, Payne J, et al. Suboptimal outcomes and treatment burden of anti-vascular endothelial growth factor treatment for diabetic macular oedema in phakic patients[J]. Eye (Lond), 2024, 38(1): 215-223. Karti O, Saatci AO. Place of intravitreal dexamethasone implant in the treatment armamentarium of diabetic macular edema[J]. World J Diabetes, 2021, 12(8): 1220-1232. de Carlo TE, Romano A, Waheed NK, et al. A review of optical coherence tomography angiography (OCTA)[J]. Int J Retina Vitreous, 2015, 1: 5. Koutsiaris AG, Batis V, Liakopoulou G, et al. Optical Coherence Tomography Angiography (OCTA) of the eye: A review on basic principles, advantages, disadvantages and device specifications[J]. Clin Hemorheol Microcirc, 2023, 83(3): 247-271. Tang J, Kern TS. Inflammation in diabetic retinopathy[J]. Prog Retin Eye Res, 2011, 30(5): 343-358. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Published Journal Publication published 11 Aug, 2025 Read the published version in BMC Ophthalmology → Version 1 posted Editorial decision: Revision requested 08 May, 2025 Reviewers agreed at journal 24 Apr, 2025 Reviews received at journal 24 Apr, 2025 Reviewers agreed at journal 23 Apr, 2025 Reviewers invited by journal 21 Apr, 2025 Submission checks completed at journal 16 Apr, 2025 First submitted to journal 09 Apr, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-6171645","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":445933969,"identity":"84f7fbb1-1b43-4c48-a858-1beeb518b713","order_by":0,"name":"Yao Shen","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAxElEQVRIiWNgGAWjYBACfv7mA4d/GNTI8bM3EKlFcsaxxMMMBceMJXsOEKnF4ECO8mGGD8yJG24kEGtLwxmGwwUGbMYMNx9vvMFQYxNNUAs/c++BwzMMZOQYZ6cVWzAcS8ttIGzLuYQDPEBbmKVzzCQYGw4T1gL0iwFQC3Nim+QZErQcBmnpkeAhUgswkBMOzjA4ZizBA/RLAjF+AUbl4Q8f/tTI2R8/vPHGhxobwlpQHCmRQIpyiBZSdYyCUTAKRsHIAAA9TURYqIpagwAAAABJRU5ErkJggg==","orcid":"","institution":"Affiliated Hospital of Nantong University","correspondingAuthor":true,"prefix":"","firstName":"Yao","middleName":"","lastName":"Shen","suffix":""},{"id":445933970,"identity":"4e73cb7f-2e1b-4e86-a10e-8ad14198a105","order_by":1,"name":"Xi Zhu","email":"","orcid":"","institution":"Affiliated Hospital of Nantong University","correspondingAuthor":false,"prefix":"","firstName":"Xi","middleName":"","lastName":"Zhu","suffix":""},{"id":445933971,"identity":"17ac5dd2-0f9a-420b-9f5e-475f9144fe1d","order_by":2,"name":"Aiqiu Li","email":"","orcid":"","institution":"Affiliated Hospital of Nantong University","correspondingAuthor":false,"prefix":"","firstName":"Aiqiu","middleName":"","lastName":"Li","suffix":""},{"id":445933972,"identity":"1b6bc8ce-6cb8-48c9-8569-af3fdd9c90b6","order_by":3,"name":"Min Ji","email":"","orcid":"","institution":"Affiliated Hospital of Nantong University","correspondingAuthor":false,"prefix":"","firstName":"Min","middleName":"","lastName":"Ji","suffix":""},{"id":445933973,"identity":"5e1cd7a6-d6aa-4c7e-a71a-e5e8c8227ef4","order_by":4,"name":"Huaijin Guan","email":"","orcid":"","institution":"Affiliated Hospital of Nantong University","correspondingAuthor":false,"prefix":"","firstName":"Huaijin","middleName":"","lastName":"Guan","suffix":""}],"badges":[],"createdAt":"2025-03-06 14:53:23","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6171645/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6171645/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1186/s12886-025-04264-9","type":"published","date":"2025-08-11T15:57:49+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":81694181,"identity":"8c3481b8-b5d4-489b-8f06-1ee1fd410cb7","added_by":"auto","created_at":"2025-04-30 11:52:41","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":450167,"visible":true,"origin":"","legend":"\u003cp\u003eThree intraoperative fundus examination techniques. \u003cstrong\u003e1A\u003c/strong\u003e demonstrates fundus observation using a 25G optical fiber; \u003cstrong\u003e1B\u003c/strong\u003e illustrates wide-angle retinal photography; and \u003cstrong\u003e1C\u003c/strong\u003e depicts intraoperative OCT imaging of the fundus.\u003c/p\u003e","description":"","filename":"floatimage1.png","url":"https://assets-eu.researchsquare.com/files/rs-6171645/v1/f37fdd26f0262aa7306d4a7d.png"},{"id":81692861,"identity":"ca61f91e-3718-438b-b188-cd03d1ac0d98","added_by":"auto","created_at":"2025-04-30 11:44:40","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":252204,"visible":true,"origin":"","legend":"\u003cp\u003eIntraoperative fundus observation using a 25G light guide fiber and corneal contact lens in four patients with diabetes and cataract, whose fundus were preoperatively obscured. \u003cstrong\u003e2A\u003c/strong\u003e reveals scattered hemorrhages in the macular area; \u003cstrong\u003e2B\u003c/strong\u003e displays flame-shaped hemorrhages around the optic disc; \u003cstrong\u003e2C\u003c/strong\u003e demonstrates extensive hard exudates; and \u003cstrong\u003e2D\u003c/strong\u003e highlights hard exudates localized to the macula.\u003c/p\u003e","description":"","filename":"floatimage2.png","url":"https://assets-eu.researchsquare.com/files/rs-6171645/v1/741366b0d25d883b7860953a.png"},{"id":81695586,"identity":"9d7675f5-2f22-4fae-bf32-e8a001aec574","added_by":"auto","created_at":"2025-04-30 12:00:41","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":557504,"visible":true,"origin":"","legend":"\u003cp\u003eIntraoperative fundus observation using the SW-8000 wide-field probe in two patients with diabetes and cataract, whose fundus were preoperatively obscured. \u003cstrong\u003e3A\u003c/strong\u003e depicts the right eye, showing scattered hemorrhages and hard exudates in the macular area; \u003cstrong\u003e3B\u003c/strong\u003e illustrates the left eye, with hard exudates localized to the macula.\u003c/p\u003e","description":"","filename":"floatimage3.png","url":"https://assets-eu.researchsquare.com/files/rs-6171645/v1/bb289da544c1325dc0aab163.png"},{"id":81694184,"identity":"2239e7c5-4cdf-4a9e-8621-05295c1191b0","added_by":"auto","created_at":"2025-04-30 11:52:41","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":267647,"visible":true,"origin":"","legend":"\u003cp\u003eIntraoperative fundus observation using the iVue OCT in two patients with diabetes and cataract, whose fundus were preoperatively obscured. \u003cstrong\u003e4A\u003c/strong\u003e demonstrates cystic macular edema; \u003cstrong\u003e4B\u003c/strong\u003ereveals macular edema with central involvement.\u003c/p\u003e","description":"","filename":"floatimage4.png","url":"https://assets-eu.researchsquare.com/files/rs-6171645/v1/88e99a9a277acc104bb9316a.png"},{"id":89310578,"identity":"4328f652-c8eb-40ae-aa83-75285d8606bc","added_by":"auto","created_at":"2025-08-18 16:08:22","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":2316947,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6171645/v1/e3339ccb-895e-4a49-a323-fe1a31e6e86f.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Effect of combined mature cataract surgery and intravitreal ranibizumab injection in eyes with pre-existing diabetic macular edema","fulltext":[{"header":"Short Summary","content":"\u003cp\u003eThis study demonstrates that timely diagnosis and treatment of diabetic macular edema (DME) during cataract surgery significantly improves short-term postoperative visual outcomes.\u003c/p\u003e"},{"header":"1 Introduction","content":"\u003cp\u003eThe global prevalence of diabetes, longer life expectancies, and an aging population are expected to significantly increase cataract surgery rates among diabetic patients\u003csup\u003e[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]\u003c/sup\u003e. Diabetics face a higher risk of postoperative complications, particularly in the presence of unstable hyperglycemia, reduced corneal endothelial cell counts, diabetic retinopathy (DR), or diabetic macular edema (DME)\u003csup\u003e[\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]\u003c/sup\u003e. Approximately 10% of diabetic patients develop DME, and when combined with cataracts, vision loss can severely impact daily life\u003csup\u003e[\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]\u003c/sup\u003e. Currently, there are no specific guidelines for managing DME during cataract surgery. While surgical intervention effectively treats diabetic cataracts, performing surgery without addressing DME may accelerate retinal disease progression, compromising postoperative vision. Conversely, delaying cataract surgery to treat DME first can hinder retinal monitoring and increase surgical complexity as the cataract worsens. Thus, managing diabetic cataracts with concurrent retinal disease remains a significant challenge for ophthalmologists.\u003c/p\u003e \u003cp\u003eA unique aspect of our study is the focus on patients with preoperatively obscured fundus due to advanced cataracts, a population often excluded from prior research due to the inability to perform high-quality preoperative retinal imaging. In these patients, traditional preoperative fundus examination is often impossible, leading to delayed diagnosis and treatment of DME. This delay can result in irreversible ocular complications and suboptimal visual outcomes\u003csup\u003e[\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]\u003c/sup\u003e. To address this critical gap, we have developed an innovative approach that combines cataract surgery with real-time intraoperative retinal examination techniques, enabling immediate diagnosis and intervention for DME during the surgical procedure\u003csup\u003e[\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eDuring the perioperative period, several treatment options are available for DME, including intravitreal anti-VEGF agents, steroids, and laser photocoagulation. Anti-VEGF therapy, supported by extensive literature, has revolutionized DME management globally\u003csup\u003e[\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]\u003c/sup\u003e. Recent studies have highlighted the protective and beneficial effects of intravitreal injections administered during cataract surgery\u003csup\u003e[\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]\u003c/sup\u003e. Previous studies have demonstrated that intravitreal ranibizumab injection immediately after cataract surgery or within the first postoperative week can effectively prevent or treat diabetic macular edema (DME) in patients with diabetic retinopathy\u003csup\u003e[\u003cspan additionalcitationids=\"CR7\" citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]\u003c/sup\u003e. Unlike previous studies, our research innovatively combined three intraoperative retinal examination techniques, enabling real preoperatively obscured fundus-time observation and evaluation of retinal conditions during cataract surgery, particularly in patients with obscured fundi\u003csup\u003e[\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]\u003c/sup\u003e. This approach is particularly valuable for patients with advanced cataracts, where traditional preoperative fundus examination is often impossible .\u003c/p\u003e \u003cp\u003eThe present study aims to evaluate the functional and anatomical outcomes of combined cataract surgery and intravitreal anti-VEGF injection in eyes with pre-existing DME and preoperatively obscured fundus. By focusing on this specific patient population, our research addresses a critical gap in clinical practice, offering a novel strategy for timely diagnosis and intervention during cataract surgery.\u003c/p\u003e"},{"header":"2 Materials and Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003e2.1 Patients\u003c/h2\u003e \u003cp\u003eA total of 350 eyes with diabetic cataracts and preoperatively obscured fundus were screened for this study. Among these, 48 eyes were identified with diabetic macular edema (DME) during intraoperative examination. After excluding 9 eyes lost to follow-up, 39 eyes meeting the inclusion/exclusion criteria were included in the final analysis. The detection rate of DME in patients with preoperatively obscured fundus was 13.7% (48/350).\u003c/p\u003e \u003cp\u003eThis prospective randomized study included consecutive patients who underwent combined cataract surgery and intravitreal treatment at our institution between January 2021 and January 2022. The study adhered to institutional and governmental ethical guidelines and was conducted in accordance with the Declaration of Helsinki (1964) and its later amendments. Ethical approval was obtained from the Institutional Ethics Committee of the Affiliated Hospital of Nantong University, and all participants provided written informed consent using a form specifically designed and approved by the Eye Institute for prospective studies.\u003c/p\u003e \u003cp\u003ePatients were eligible if they had a preoperative diagnosis of diabetic cataract with poor fundus visualization, intraoperative evidence of diabetic macular edema (DME), or moderate-to-severe diabetic retinopathy (DR). Exclusion criteria included intravitreal injection within the preceding 5 months, concurrent retinal diseases (e.g., active PDR level with new vessels in the disc and retina or vitreous hemorrhageretinal vein occlusion, retinal dystrophies, or age-related macular degeneration), glaucoma, or previous vitrectomy. Participants were informed that they would be randomly assigned to one of two groups using a random number table.\u003c/p\u003e \u003cp\u003eFor the 7 patients with bilateral involvement, the second eye was enrolled only after the first eye completed the 12-week follow-up, and treatment allocation (ranibizumab/delayed) was randomized independently for each eye to minimize intra-patient correlation. Patients in the delayed treatment group were informed during the first postoperative week that they would receive intravitreal injections for DME management. Based on previous studies demonstrating the efficacy of intravitreal ranibizumab injection immediately after cataract surgery or within the first postoperative week, and considering that our patients had advanced cataracts with preoperatively obscured fundus, significant phacoemulsification energy usage during surgery, and a higher likelihood of postoperative corneal edema, we chose to administer treatment for macular edema at 4 weeks postoperatively in the delayed group and completed follow-up assessments\u003csup\u003e[\u003cspan additionalcitationids=\"CR7\" citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]\u003c/sup\u003e. Our delayed treatment group intentionally included both protocol-driven and financially constrained subgroups to reflect real-world practice challenges.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003e2.2 Preoperative Evaluation and Follow-Up\u003c/h2\u003e \u003cp\u003ePrior to cataract surgery, all patients underwent comprehensive ophthalmic evaluations, including slit-lamp examination, dilated fundus examination, non-contact tonometry for intraocular pressure (IOP), fundus B-scan ultrasonography and optical coherence tomography (OCT). Preoperative OCT was attempted but deemed unreliable due to media opacity; definitive imaging was obtained. Visual acuity was assessed using the Early Treatment Diabetic Retinopathy Study (ETDRS) scale, and diabetic retinopathy (DR) severity was graded according to the Diabetic Retinopathy Study (DRS) criteria. Postoperative follow-up examinations were conducted at 1 week, 1 month, and 3 months, with each visit including a complete ophthalmologic evaluation.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003e2.3 Surgical Technique\u003c/h2\u003e \u003cp\u003eAll surgeries were performed by three experienced surgeons using a standardized technique under topical anesthesia. A 2.4-mm temporal clear corneal incision was made, followed by continuous curvilinear capsulorhexis. After hydrodissection, phacoemulsification of the nucleus and cortical aspiration were performed. Prior to intraocular lens (IOL) implantation, the fundus was examined using multiple approaches\u003csup\u003e[\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]\u003c/sup\u003e, and patients in the intervention group were randomized based on the findings. In the intervention group, a distance gauge was used to mark a point 4 mm from the corneoscleral rim in the inferotemporal quadrant. A needle was inserted vertically at the mark, and ranibizumab was slowly injected into the vitreous cavity. The needle was then withdrawn, and the injection site was moistened with sodium lactate Ringer's solution and gently compressed with a swab. Tobramycin-dexamethasone ophthalmic ointment was applied to the conjunctival sac, and the eye was covered with gauze before the patient was transferred to the ward.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003e2.4 Postoperative Medication:\u003c/h2\u003e \u003cp\u003eAll patients received the same postoperative medication regimen: topical fluoroquinolone four times daily for one week, topical dexamethasone four times daily for one week (tapered over the following two weeks), and a topical nonsteroidal anti-inflammatory drug for three weeks.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003e2.5 Intraoperative Retinal Examination:\u003c/h2\u003e \u003cp\u003eFollowing routine surface anesthesia, a limbal incision was made, and continuous curvilinear capsulorhexis was performed. The lens was separated using irrigation, followed by phacoemulsification and cortical aspiration. Each imaging modality added approximately 3\u0026ndash;5 minutes to surgery time, with no reported patient discomfort under topical anesthesia.\u003c/p\u003e \u003cdiv id=\"Sec8\" class=\"Section3\"\u003e \u003ch2\u003e2.5.1 25G Optical Fiber with Corneal Contact Lens:\u003c/h2\u003e \u003cp\u003eAfter removing the opaque crystalline lens and aspirating residual cortex, viscoelastic was injected into the anterior chamber. A sterile 25G optical fiber was inserted through the main corneal incision (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eA), and a corneal contact lens (11D flat-concave) coated with viscoelastic was placed on the cornea. The microscope light was turned off, and the focus was adjusted to visualize the posterior pole. Surgical forceps were used to gently manipulate the eye for peripheral retinal observation. Findings were photographed and recorded (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec9\" class=\"Section3\"\u003e \u003ch2\u003e2.5.2 SW-8000 Wide-Angle Probe Camera:\u003c/h2\u003e \u003cp\u003eAfter removing the optical fiber and washing away residual viscoelastic, a sterile SW-8000 probe camera (SW-8000, Tianjin Suowei Electronic Technology Co.,Ltd) was positioned vertically above the cornea (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eB). The optic disc, macula, and retinal quadrants (temporal, superior, nasal, and inferior) were sequentially examined on the screen, and images were captured for documentation (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec10\" class=\"Section3\"\u003e \u003ch2\u003e\u003cb\u003e2.5.3 iVue OCT\u003c/b\u003e (\u003cb\u003eOptovue, Inc., Fremont, CA, USA\u003c/b\u003e):\u003c/h2\u003e \u003cp\u003eFollowing IOL implantation, the iOCT was used to evaluate the macular layers (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eC). Images were captured and recorded for analysis (Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eBased on intraoperative retinal examination findings, eligible patients were randomized into groups. For those requiring pharmacological intervention, intravitreal ranibizumab injection was administered after obtaining informed consent and completing cataract surgery.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003e2.6 Statistical Analysis\u003c/h2\u003e \u003cp\u003eNumerical data were summarized as means\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation (SD) if normally distributed, or as medians with interquartile ranges (IQR) if non-normally distributed. Categorical data were presented as frequencies and percentages. Normality of data distribution was assessed using the Shapiro-Wilk test. For non-normally distributed numerical variables, between-group comparisons were performed using the Mann-Whitney U test or Kruskal-Wallis test, as appropriate. Within-group comparisons for non-normally distributed variables were analyzed using the Friedman test for repeated measures. Categorical data were compared using the chi-square test or Fisher\u0026rsquo;s exact test, depending on the sample size. All statistical tests were two-sided, and a P value\u0026thinsp;\u0026lt;\u0026thinsp;0.05 was considered statistically significant.\u003c/p\u003e \u003cp\u003eMissing data were addressed using multiple imputation methods, assuming data were missing at random (MAR). Sensitivity analyses were conducted to evaluate the impact of missing data on the results. For variables with more than 10% missing values, complete case analysis was performed to ensure robustness of the findings. Statistical analyses were conducted using SPSS version 25.0 (IBM Corp., Armonk, NY, USA) and R software (version 4.0.3, R Foundation for Statistical Computing, Vienna, Austria).\u003c/p\u003e \u003c/div\u003e"},{"header":"3 Results","content":"\u003cp\u003eA total of 65 eyes from 39 patients who underwent combined cataract surgery and intravitreal treatment were initially enrolled. Of these, 10 eyes were excluded for not meeting inclusion criteria, 6 were lost to follow-up, and 10 were withdrawn upon request. Ultimately, 39 eyes meeting the inclusion/exclusion criteria were included in the final analysis. All 65 eyes underwent successful surgery without intraoperative or postoperative complications. Intravitreal treatment was administered as a standard injection at the conclusion of surgery, with 20 eyes receiving ranibizumab and 19 eyes assigned to the untreated group.\u003c/p\u003e \u003cp\u003eA total of 350 eyes with diabetic cataracts and preoperatively obscured fundus were screened, of which 48 eyes (13.7%) were identified with diabetic macular edema (DME) during intraoperative examination. After excluding 9 eyes lost to follow-up, 39 eyes were included in the final analysis. As shown in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e, the clinical characteristics of the 32 patients at screening demonstrated no significant differences between the two groups in terms of gender distribution, age, duration of diabetes, insulin use, history of panretinal photocoagulation (PRP), best-corrected visual acuity (BCVA), intraocular pressure (IOP), central subfield thickness (CST), or total macular volume (TMV). Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e summarizes the BCVA, CST, and TMV values for the 32 patients at each follow-up time point (1 week, 4 weeks, and 12 weeks).\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 Patient Characteristics\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=\"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=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCharacteristic\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eRanibizumab (N\u0026thinsp;=\u0026thinsp;20)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eDelayed (N\u0026thinsp;=\u0026thinsp;19)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cem\u003eP\u003c/em\u003e\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMale: female\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e11:9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6:13\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.1\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\u003e62.2\u0026thinsp;\u0026plusmn;\u0026thinsp;13.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e59.9\u0026thinsp;\u0026plusmn;\u0026thinsp;10.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.6\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDuration of diabetes, years\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e10.2\u0026thinsp;\u0026plusmn;\u0026thinsp;4.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e10.3\u0026thinsp;\u0026plusmn;\u0026thinsp;2.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.5\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eInsulin used, (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7(35)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7(37)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.7\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHypertension, No. (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e10(60)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e9(47)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePRP history, (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5(25)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2(11)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBCVA, ETDRS letters\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e35.9\u0026thinsp;\u0026plusmn;\u0026thinsp;15.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e37.8\u0026thinsp;\u0026plusmn;\u0026thinsp;15.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.8\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIOP, mmHg\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e16.2\u0026thinsp;\u0026plusmn;\u0026thinsp;2.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e16.2\u0026thinsp;\u0026plusmn;\u0026thinsp;2.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.9\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCST, \u0026micro;m\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e343.2\u0026thinsp;\u0026plusmn;\u0026thinsp;121.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e312.7\u0026thinsp;\u0026plusmn;\u0026thinsp;107.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.6\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTMV, mm\u003csup\u003e3\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e10.5\u0026thinsp;\u0026plusmn;\u0026thinsp;1.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e10.5\u0026thinsp;\u0026plusmn;\u0026thinsp;1.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.9\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 \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\u003ePostoperative BCVA, CST, and TMV*\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"7\"\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 \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003eBCVA\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003eCST\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c7\" namest=\"c6\"\u003e \u003cp\u003eTMV\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\u003eRanibizumab\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eDelayed\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eRanibizumab\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eDelayed\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eRanibizumab\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eDelayed\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e1 Week\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e65.4\u0026thinsp;\u0026plusmn;\u0026thinsp;10.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e61.7\u0026thinsp;\u0026plusmn;\u0026thinsp;15.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e283.2\u0026thinsp;\u0026plusmn;\u0026thinsp;65.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e293.4\u0026thinsp;\u0026plusmn;\u0026thinsp;86.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e11.0\u0026thinsp;\u0026plusmn;\u0026thinsp;1.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e11.0\u0026thinsp;\u0026plusmn;\u0026thinsp;1.1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e4 weeks\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e69.2\u0026thinsp;\u0026plusmn;\u0026thinsp;9.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e62.6\u0026thinsp;\u0026plusmn;\u0026thinsp;18.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e295.5\u0026thinsp;\u0026plusmn;\u0026thinsp;64.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e320.6\u0026thinsp;\u0026plusmn;\u0026thinsp;113.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e11.0\u0026thinsp;\u0026plusmn;\u0026thinsp;1.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e11.3\u0026thinsp;\u0026plusmn;\u0026thinsp;1.2\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e12 weeks\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e70.6\u0026thinsp;\u0026plusmn;\u0026thinsp;10.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e61.1\u0026thinsp;\u0026plusmn;\u0026thinsp;16.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e275.0\u0026thinsp;\u0026plusmn;\u0026thinsp;54.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e346.5\u0026thinsp;\u0026plusmn;\u0026thinsp;108.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e11.2\u0026thinsp;\u0026plusmn;\u0026thinsp;1.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e11.7\u0026thinsp;\u0026plusmn;\u0026thinsp;1.2\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*The units of BCVA, CST, and TMV are ETDRS letter numbers, \u0026micro;m, and mm\u003csup\u003e3\u003c/sup\u003e, respectively.\u003c/p\u003e \u003cdiv id=\"Sec13\" class=\"Section2\"\u003e \u003ch2\u003e3.1. Change in BCVA, Relative to Baseline\u003c/h2\u003e \u003cp\u003eThe two groups exhibited clinically significant differences in terms of the change of BCVA from baseline at 3-month follow-up visits (P\u0026thinsp;=\u0026thinsp;0.04, Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e).\u003c/p\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\u003eMean Changes in BCVA From Baseline\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=\"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 \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colspan=\"3\" nameend=\"c4\" namest=\"c2\"\u003e \u003cp\u003eChanges in BCVA From Baseline\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\u003eRanibizumab\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eDelayed\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eP\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e1week\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e29.4\u0026thinsp;\u0026plusmn;\u0026thinsp;16.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e23.9\u0026thinsp;\u0026plusmn;\u0026thinsp;10.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e4 weeks\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e33.2\u0026thinsp;\u0026plusmn;\u0026thinsp;15.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e24.8\u0026thinsp;\u0026plusmn;\u0026thinsp;13.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e12 weeks\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e34.6\u0026thinsp;\u0026plusmn;\u0026thinsp;15.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e23.3\u0026thinsp;\u0026plusmn;\u0026thinsp;14.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.04*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec14\" class=\"Section2\"\u003e \u003ch2\u003e3.2. Change in Central Subfield Thickness Relative to Baseline\u003c/h2\u003e \u003cp\u003eThe two groups did not significantly differ in terms of the mean CST changes at 1-week, 4-week follow-up visits (P\u0026thinsp;=\u0026thinsp;0.08 and 0.2, respectively, Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e). However, there was a significant clinical difference between the two groups during 3-month follow-up (P\u0026thinsp;=\u0026thinsp;0.05).\u003c/p\u003e \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\u003eMean Changes in CST From Baseline\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=\"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 \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colspan=\"3\" nameend=\"c4\" namest=\"c2\"\u003e \u003cp\u003eChanges in CST From Baseline\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\u003eRanibizumab\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eDelayed\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eP\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e1week\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e-60.0\u0026thinsp;\u0026plusmn;\u0026thinsp;77.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-19.3\u0026thinsp;\u0026plusmn;\u0026thinsp;59.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.08\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e4 weeks\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e-47.0\u0026thinsp;\u0026plusmn;\u0026thinsp;99.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7.95\u0026thinsp;\u0026plusmn;\u0026thinsp;103.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.2\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e12 weeks\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e-68.2\u0026thinsp;\u0026plusmn;\u0026thinsp;116.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e33.8\u0026thinsp;\u0026plusmn;\u0026thinsp;143.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.05*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec15\" class=\"Section2\"\u003e \u003ch2\u003e3.3. Change in Total Macular Volume Relative to Baseline\u003c/h2\u003e \u003cp\u003eThe trend of TMV changes in the two groups is similar, and no statistical significance was found after comparison (P\u0026thinsp;=\u0026thinsp;0.8, 0.4, and 0.2, respectively, Table\u0026nbsp;\u003cspan refid=\"Tab5\" class=\"InternalRef\"\u003e5\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab5\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 5\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eMean Changes in TMV From Baseline\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=\"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 \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colspan=\"3\" nameend=\"c4\" namest=\"c2\"\u003e \u003cp\u003eChanges in CST From Baseline\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\u003eRanibizumab\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eDelayed\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eP\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e1week\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.48\u0026thinsp;\u0026plusmn;\u0026thinsp;1.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.50\u0026thinsp;\u0026plusmn;\u0026thinsp;1.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.8\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e4 weeks\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.45\u0026thinsp;\u0026plusmn;\u0026thinsp;1.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.73\u0026thinsp;\u0026plusmn;\u0026thinsp;1.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.4\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e12 weeks\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.69\u0026thinsp;\u0026plusmn;\u0026thinsp;1.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.1\u0026thinsp;\u0026plusmn;\u0026thinsp;1.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.2\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec16\" class=\"Section2\"\u003e \u003ch2\u003e3.4. Safety of Ranibizumab Injection\u003c/h2\u003e \u003cp\u003eConsidering adverse events, two occurred in the ranibizumab injection group. They were both associated with high postoperative IOP at one week. After timely intervention with ocular hypotensive therapy, there were no more serious complications in these patients.\u003c/p\u003e \u003cp\u003eWe did not systematically evaluate pseudophakic CME incidence due to challenges in differentiating postoperative inflammation-mediated edema from pre-existing DME progression. Future studies should employ FA or en face OCT to dissect these mechanisms.\u003c/p\u003e \u003c/div\u003e"},{"header":"4 Discussion","content":"\u003cp\u003eThe primary focus of this study was to evaluate the efficacy and safety of intravitreal anti-VEGF drug injection during cataract surgery in patients with pre-existing diabetic macular edema (DME). Our findings align with previous research indicating that cataract surgery in diabetic patients can exacerbate DME, primarily due to metabolic dysregulation, retinal microcirculation changes, and inflammatory responses\u003csup\u003e[\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]\u003c/sup\u003e. However, unlike many studies that exclude patients with significant optical media opacities, our study specifically targeted patients with obscured fundi, utilizing innovative intraoperative retinal examination techniques to enable real-time diagnosis and intervention. This approach addresses a critical gap in clinical practice, as delayed DME detection and treatment can lead to irreversible ocular complications\u003csup\u003e[\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eThe rationale for intraoperative anti-VEGF injection stems from reports that cataract surgery alone may transiently worsen DME in diabetic patients due to inflammatory and metabolic perturbations\u003csup\u003e[\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]\u003c/sup\u003e. Our study observed that combined surgery and ranibizumab therapy attenuated this effect, as evidenced by greater BCVA improvement and CST reduction compared to delayed treatment. However, our study diverges from some earlier findings in that changes in retinal thickness did not reach statistical significance, possibly due to the preoperative inability to accurately measure retinal thickness in patients with advanced cataracts\u003csup\u003e[\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]\u003c/sup\u003e. This highlights the importance of intraoperative imaging techniques in guiding treatment decisions .\u003c/p\u003e \u003cp\u003eCurrent DME management includes anti-VEGF therapy, corticosteroids, laser photocoagulation, and surgical interventions. While anti-VEGF agents have become the first-line treatment due to their efficacy in reducing vascular leakage and edema, their short duration of action and high cost remain limitations\u003csup\u003e[\u003cspan additionalcitationids=\"CR12\" citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]\u003c/sup\u003e. Corticosteroids, such as the sustained-release dexamethasone implant (Ozurdex\u0026reg;) and fluocinolone acetonide implant (Iluvien\u0026reg;), offer an alternative by providing prolonged anti-inflammatory effects with less frequent dosing\u003csup\u003e[\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]\u003c/sup\u003e. These agents may be particularly beneficial in patients with chronic DME or those who cannot comply with frequent anti-VEGF injections. However, their use is often limited by the risk of intraocular pressure elevation and cataract progression\u003csup\u003e[\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]\u003c/sup\u003e. Recent trials further highlight the role of sustained-release corticosteroids in stabilizing macular anatomy and reducing retreatment frequency\u003csup\u003e[\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]\u003c/sup\u003e. Laser therapy, once the gold standard, has been largely supplanted by pharmacologic treatments but remains valuable in specific cases\u003csup\u003e[\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]\u003c/sup\u003e. Our study supports the use of intravitreal anti-VEGF injections during cataract surgery as a viable strategy to improve visual outcomes and control DME progression\u003csup\u003e[\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eThe timing of intravitreal ranibizumab injection in the delayed group was set at 4 weeks postoperatively, based on previous studies demonstrating the efficacy of immediate or early postoperative anti-VEGF therapy\u003csup\u003e[\u003cspan additionalcitationids=\"CR7\" citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]\u003c/sup\u003e. Additionally, our patients had advanced cataracts with preoperatively obscured fundus, which required significant phacoemulsification energy during surgery, leading to a higher likelihood of postoperative corneal edema. Delaying treatment until 4 weeks postoperatively allowed for the resolution of early postoperative inflammation and corneal edema, ensuring more accurate assessment and treatment of macular edema.\u003c/p\u003e \u003cp\u003eThe 4-week delay in the control group was designed to balance two factors: (a) the need to resolve early postoperative inflammation and corneal edema for accurate DME assessment, and (b) minimizing potential harm from treatment delay. Existing evidence suggests that short-term delays (\u0026le;\u0026thinsp;1 month) in initiating anti-VEGF therapy for DME do not preclude good long-term outcomes if subsequent treatment is consistent\u003csup\u003e[\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]\u003c/sup\u003e. In our cohort, despite the delay, no eyes developed irreversible structural sequelae (e.g., ellipsoid zone disruption on OCT), though longer follow-up is needed to confirm this observation.\"\u003c/p\u003e \u003cp\u003eThis study has several limitations. First, the small sample size (39 eyes) may limit the generalizability of our findings. Future studies should expand the cohort to include a more diverse patient population and conduct subgroup analyses to identify specific patient profiles that benefit most from combined cataract surgery and anti-VEGF therapy. Second, the 12-week follow-up period is relatively short, and longer-term studies are needed to assess the durability of treatment effects and potential late complications\u003csup\u003e[\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]\u003c/sup\u003e. Third, when accounting for intra-patient correlation using mixed-effects models, the statistical significance of some outcomes was attenuated (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026gt;\u0026thinsp;0.05), likely due to reduced power from the smaller effective sample size in this analysis. However, the preservation of effect sizes (e.g., consistent BCVA letter gains) suggests that the clinical relevance of combined therapy warrants further validation in larger cohorts with unilateral involvement. Finally, our study focused solely on ranibizumab; future research should compare the efficacy of different anti-VEGF agents, corticosteroids, and combination therapies to optimize treatment protocols\u003csup\u003e[\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e, \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eAdditionally, incorporating advanced imaging modalities such as optical coherence tomography angiography (OCTA) and inflammatory biomarker analysis could provide deeper insights into disease mechanisms and guide more personalized treatment approaches\u003csup\u003e[\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e, \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]\u003c/sup\u003e. For example, staging DME based on OCT and OCTA findings may help tailor interventions to individual patient needs, while pre-operative testing of inflammatory factors could identify patients who would benefit from adjunctive anti-inflammatory therapy\u003csup\u003e[\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e, \u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]\u003c/sup\u003e. Future studies should explore these strategies to optimize treatment protocols and improve patient outcomes\u003csup\u003e[\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eData Availability\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe data that support the findings of this study are available from the corresponding author upon reasonable request.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthical Approval\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the Ethics Committee of the Affiliated Hospital of Nantong University. The trial registration number is 2019-K068.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eInformed consent was obtained from all participating subjects after they were given an explanation of the study.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflicts of Interest\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no conflicts of interest.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgments\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eI extend my heartfelt gratitude to all colleagues for their meticulous efforts and professional dedication during the fieldwork execution. Particular recognition is owed to my research supervisor, whose scholarly insights critically shaped the manuscript\u0026apos;s analytical rigor. This dataset\u0026apos;s enhanced validity fundamentally derives from our collaborative intellectual enterprise, wherein each contributor\u0026apos;s expertise served as an indispensable epistemic pillar.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis work was supported by Nantong Municipal Science and Technology Project (No. MS22022020).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor Contribution\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eYao Shen and Xi Zhu wrote the main manuscript text and Aiqiu Li prepared figures. Min Ji and Huaijin Guan reviewed the manuscript.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eChan LKY, Lin SS, Chan F, et al. Optimizing treatment for diabetic macular edema during cataract surgery[J]. Front Endocrinol (Lausanne), 2023, 14: 1106706.\u003c/li\u003e\n\u003cli\u003eWang W, Lo ACY. Diabetic Retinopathy: Pathophysiology and Treatments[J]. Int J Mol Sci, 2018, 19(6).\u003c/li\u003e\n\u003cli\u003ePatel JI, Hykin PG, Cree IA. Diabetic cataract removal: postoperative progression of maculopathy--growth factor and clinical analysis[J]. Br J Ophthalmol, 2006, 90(6): 697-701.\u003c/li\u003e\n\u003cli\u003eSu Shu WS, Wu Jian, et al. Feasibility and clinical significance of intraoperative real-time fundus examination in cataractous eyes. In: Chin J Exp Ophthalmol, Vol. 04, 2020: 331-335.\u003c/li\u003e\n\u003cli\u003eSu S, Wu J, Ji M, et al. [A comparative study of three intraoperative real-time fundus examinations in cataractous eyes][J]. Zhonghua Yan Ke Za Zhi, 2021, 57(11): 850-856.\u003c/li\u003e\n\u003cli\u003eUdaondo P, Garcia-Pous M, Garcia-Delpech S, et al. Prophylaxis of macular edema with intravitreal ranibizumab in patients with diabetic retinopathy after cataract surgery: a pilot study[J]. J Ophthalmol, 2011, 2011: 159436.\u003c/li\u003e\n\u003cli\u003eZhao LQ, Cheng JW. A Systematic Review and Meta-Analysis of Clinical Outcomes of Intravitreal Anti-VEGF Agent Treatment Immediately after Cataract Surgery for Patients with Diabetic Retinopathy[J]. J Ophthalmol, 2019, 2019: 2648267.\u003c/li\u003e\n\u003cli\u003eStarr MR, Mahr MA, Smith WM, et al. Outcomes of Patients With Active Diabetic Macular Edema at the Time of Cataract Surgery Managed With Intravitreal Anti-Vascular Endothelial Growth Factor Injections[J]. Am J Ophthalmol, 2021, 229: 194-199.\u003c/li\u003e\n\u003cli\u003eWu J, Zhong Y, Yue S, et al. Aqueous Humor Mediator and Cytokine Aberrations in Diabetic Retinopathy and Diabetic Macular Edema: A Systematic Review and Meta-Analysis[J]. Dis Markers, 2019, 2019: 6928524.\u003c/li\u003e\n\u003cli\u003eBoyer DS, Yoon YH, Belfort R, Jr., et al. Three-year, randomized, sham-controlled trial of dexamethasone intravitreal implant in patients with diabetic macular edema[J]. Ophthalmology, 2014, 121(10): 1904-1914.\u003c/li\u003e\n\u003cli\u003eSchmidt-Erfurth U, Garcia-Arumi J, Bandello F, et al. Guidelines for the Management of Diabetic Macular Edema by the European Society of Retina Specialists (EURETINA)[J]. Ophthalmologica, 2017, 237(4): 185-222.\u003c/li\u003e\n\u003cli\u003eBrown DM, Emanuelli A, Bandello F, et al. KESTREL and KITE: 52-Week Results From Two Phase III Pivotal Trials of Brolucizumab for Diabetic Macular Edema[J]. Am J Ophthalmol, 2022, 238: 157-172.\u003c/li\u003e\n\u003cli\u003eWykoff CC, Garweg JG, Regillo C, et al. KESTREL and KITE Phase 3 Studies: 100-Week Results With Brolucizumab in Patients With Diabetic Macular Edema[J]. Am J Ophthalmol, 2024, 260: 70-83.\u003c/li\u003e\n\u003cli\u003eCampochiaro PA, Marcus DM, Awh CC, et al. The Port Delivery System with Ranibizumab for Neovascular Age-Related Macular Degeneration: Results from the Randomized Phase 2 Ladder Clinical Trial[J]. Ophthalmology, 2019, 126(8): 1141-1154.\u003c/li\u003e\n\u003cli\u003eYang X, Cao Y, Cao X, et al. Anti-VEGF monotherapy versus anti-VEGF therapy combined with laser or intravitreal glucocorticoid therapy for diabetic macular edema: A Bayesian network meta-analysis[J]. Diabetes Obes Metab, 2025.\u003c/li\u003e\n\u003cli\u003eWells JA, Glassman AR, Ayala AR, et al. Aflibercept, Bevacizumab, or Ranibizumab for Diabetic Macular Edema: Two-Year Results from a Comparative Effectiveness Randomized Clinical Trial[J]. Ophthalmology, 2016, 123(6): 1351-1359.\u003c/li\u003e\n\u003cli\u003eRennie C, Lotery A, Payne J, et al. Suboptimal outcomes and treatment burden of anti-vascular endothelial growth factor treatment for diabetic macular oedema in phakic patients[J]. Eye (Lond), 2024, 38(1): 215-223.\u003c/li\u003e\n\u003cli\u003eKarti O, Saatci AO. Place of intravitreal dexamethasone implant in the treatment armamentarium of diabetic macular edema[J]. World J Diabetes, 2021, 12(8): 1220-1232.\u003c/li\u003e\n\u003cli\u003ede Carlo TE, Romano A, Waheed NK, et al. A review of optical coherence tomography angiography (OCTA)[J]. Int J Retina Vitreous, 2015, 1: 5.\u003c/li\u003e\n\u003cli\u003eKoutsiaris AG, Batis V, Liakopoulou G, et al. Optical Coherence Tomography Angiography (OCTA) of the eye: A review on basic principles, advantages, disadvantages and device specifications[J]. Clin Hemorheol Microcirc, 2023, 83(3): 247-271.\u003c/li\u003e\n\u003cli\u003eTang J, Kern TS. Inflammation in diabetic retinopathy[J]. Prog Retin Eye Res, 2011, 30(5): 343-358.\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":"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":"cataract, diabetic macular edema, ranibizumab, intraoperative fundus examination","lastPublishedDoi":"10.21203/rs.3.rs-6171645/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6171645/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003ePurpose:\u003c/strong\u003e This study aimed to compare the functional and anatomical outcomes of combined cataract surgery and intravitreal ranibizumab injection in eyes with pre-existing diabetic macular edema (DME) and preoperatively obscured fundus due to advanced cataracts.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods:\u003c/strong\u003e After screening 350 eyes with diabetic cataracts and preoperatively obscured fundus, 39 eyes with intraoperatively confirmed DME were included in the final analysis. Eyes were randomly assigned to either the ranibizumab group (20 eyes) or the delayed treatment group (19 eyes). Best-corrected visual acuity (BCVA), total macular volume (TMV), and central subfield thickness (CST) were evaluated at 1, 4, and 12 weeks postoperatively. Intraoperative retinal examination techniques, including 25G optical fiber, wide-angle retinal photography, and intraoperative OCT, were used to enable real-time diagnosis and intervention.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults:\u003c/strong\u003e At 12 weeks, the ranibizumab group showed a mean BCVA improvement of 34 letters, compared to 23 letters in the delayed group (P=0.03). The mean change in CST was -68 μm in the ranibizumab group and 33 μm in the delayed group (P=0.05). Changes in TMV were similar between the two groups at 12 weeks.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion:\u003c/strong\u003e Intravitreal ranibizumab injection during cataract surgery significantly improved visual acuity and reduced central subfield thickness at 12 weeks postoperatively in patients with pre-existing DME and preoperatively obscured fundus. This study highlights the importance of intraoperative retinal examination and timely anti-VEGF intervention in improving visual outcomes for this challenging patient population.\u003c/p\u003e","manuscriptTitle":"Effect of combined mature cataract surgery and intravitreal ranibizumab injection in eyes with pre-existing diabetic macular edema","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-04-30 11:44:36","doi":"10.21203/rs.3.rs-6171645/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2025-05-08T06:34:55+00:00","index":"","fulltext":""},{"type":"reviewerAgreed","content":"62695948345213862382011116884125049418","date":"2025-04-24T08:25:41+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-04-24T07:38:29+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"10594319933129871014386656075420376836","date":"2025-04-23T22:48:08+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-04-21T20:53:59+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-04-16T06:01:24+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Ophthalmology","date":"2025-04-09T11:59:44+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":"2eb57808-c812-4499-a4d4-9b2d14f35693","owner":[],"postedDate":"April 30th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2025-08-18T16:02:44+00:00","versionOfRecord":{"articleIdentity":"rs-6171645","link":"https://doi.org/10.1186/s12886-025-04264-9","journal":{"identity":"bmc-ophthalmology","isVorOnly":false,"title":"BMC Ophthalmology"},"publishedOn":"2025-08-11 15:57:49","publishedOnDateReadable":"August 11th, 2025"},"versionCreatedAt":"2025-04-30 11:44:36","video":"","vorDoi":"10.1186/s12886-025-04264-9","vorDoiUrl":"https://doi.org/10.1186/s12886-025-04264-9","workflowStages":[]},"version":"v1","identity":"rs-6171645","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6171645","identity":"rs-6171645","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}