Subretinal Injection of Balanced Salt Solution for Macular Edema Secondary to Retinal Vein Occlusion

Subretinal Injection of Balanced Salt Solution for Macular Edema Secondary to Retinal Vein Occlusion | 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 Subretinal Injection of Balanced Salt Solution for Macular Edema Secondary to Retinal Vein Occlusion Yue Pan, Xiang Zhang, Zetong Nie, Jiaxing Chi, Chang Liu, Qinning Xie, and 4 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7385007/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Purposes : To investigate the efficacy and safety of subretinal balanced salt solution (BSS) injections for macular edema secondary to retinal vein occlusion (RVO-ME). Methods : We retrospectively analyzed 19 eyes of 19 patients characterized by Retinal vein occlusion (RVO) diagnosed usng retinal angiography and persistent or recurrent edema on OCT after at least three standard-dose Anti-vascular endothelial growth factor (anti-VEGF) treatments. The operation group received vitrectomy combined with internal limiting membrane (ILM) peeling and subretinal injection of BSS. The operation group continued to receive intravitreal injection of anti-VEGF drugs. The results of visual acuity, retinal morphology, and recurrence were analyzed and compared between the two groups after treatment. Results : The best corrected visual acuity (BCVA) of the surgery group improved (0.60 ± 0.45, P = 0.006) and the best visual acuity reached the same level as that of the injection group (0.53 ± 0.49, P = 0.622). The minimum Central macular thickness (CMT) of the two groups after intervention was 266.40 ± 52.08 µm and 221.89 ± 38.62 µm (P = 0.051), respectively, and both groups exhibited reduced CMT and edema (P < 0.001, P = 0.008). The recurrence rate of the surgery group was 40%, which was lower than that of the injection group (88.9%, P = 0.051). The CMT were 473.00 ± 45.44 µm and 586.89 ± 169.18 μm (P = 0.225) at recurrence. Conclusions : Vitrectomy with ILM peeling and subretinal BSS injection may enhance visual acuity, reduce macular edema, and lower the recurrence rate in patients with RVO-ME. Retinal vein occlusion Macular edema Subretinal injection Balanced salt solution Anti-vascular endothelial growth factor Pars plana vitrectomy Figures Figure 1 1. Introduction Retinal vein occlusion (RVO) is the second most common disease in vitreoretinopathy after diabetic retinopathy, and macular edema (ME) is the most common RVO complication, leading to visual impairment. 1 The pathogenesis of macular edema secondary to retinal vein occlusion (RVO-ME) remains unclear and is mainly related to destruction of the inner blood–retinal barrier, high vascular permeability, and increased local inflammatory response. 2 Clinically, the preferred treatment for RVO-ME is intravitreal injection of anti-vascular endothelial growth factor (anti-VEGF) drugs, which have shown long-term therapeutic effects in restoring visual function and macular morphology. 3 However, it has been observed in clinic and in some studies that the efficacy of anti-VEGF drug in ME treatment is limited in some patients, and the mechanism underlying this condition is complex. Notably, Ozurdex improves initial and refractory ME. 4 – 6 Additional approaches such as cyst resection, combination therapy with Ozurdex and anti-VEGF agents, and subthreshold micropulse laser treatment have also been used for refractory ME. 7 – 9 RVO-ME has been a very challenging issue for clinicians because it can lead to irreversible vision loss if not followed up and managed promptly, and some patients respond poorly to anti-VEGF therapy or experience recurrence after improvement. Subretinal injection of a balanced salt solution (BSS) is a novel clinical technique which has been applied in some clinical studies, and its safety and effectiveness have been confirmed. 10 – 12 Mao et al. used this technique to treat refractory diabetic macular edema (DME) and found that DME resolved significantly at 1 week and 1 month after surgery. 13 Subretinal BSS injection may reduce the colloid osmotic pressure in the retinal tissue, remove inflammatory factors and migrating cells from the retinal pigment epithelium (RPE), and reduce the production and accumulation of inflammatory factors, thus improving persistent or recurrent edema To date, no studies have specifically examined subretinal BSS injection for RVO-ME. Considering the recurrent edema of RVO-ME and the burden of continuous injection, we considered whether surgery could achieve edema resolution, visual improvement, and long-term maintenance. In this study, we investigated the efficacy of vitrectomy combined with subretinal injection of BSS compared with injection in the treatment of recurrent RVO-ME for edema resolution, visual improvement, and recurrence of edema. 2. Methods 2.1 Study Design This retrospective study was conducted at Tianjin Medical University Eye Hospital. Patients with RVO-ME were enrolled from June 2023 through December 2024. This study was conducted in accordance with the principles of the Declaration of Helsinki and was approved by the Clinical Trials Ethics Committee of Tianjin Medical University Eye Hospital (2025KY-03). 2.2 Study Population A total of 19 eyes from 19 patients were included in this study, characterized by a diagnosis of RVO on retinal angiography, confirmed presence of ME on OCT images, and persistent or recurrent edema after at least three standard doses of anti-VEGF therapy. Patients with coexisting ocular conditions (age-related macular degeneration, retinal detachment, or diabetic retinopathy) were excluded. Of the 19 patients, 10 underwent surgery and 9 underwent intravitreal injections. The surgery group underwent vitrectomy combined with internal limiting membrane (ILM) peeling and subretinal injection of BSS. The injection group continued to receive anti-VEGF therapy. 2.3 Clinical Study Protocol 2.3.1 Surgical procedure All patients of surgery group underwent surgical procedures performed by the same experienced surgeon. If the patient had significant opacification, phacoemulsification and intraocular lens implantation were performed. The surgical procedure was conducted using an OPMI LUMERA T surgical microscope. The main surgical procedure was as follows: A 25 gauge minimally invasive pars plana vitrectomy (PPV) was performed using the CONSTELLATION vitrectomy system, and complete posterior vitreous detachment was done with triamcinolone acetonide assistance. ILM approximately three optic disc diameters were peeling with the assistance of 0.025% indocyanine green staining. Subretinal injection of BSS was performed (see 2. Subretinal Injection of BSS procedure). Air-liquid exchange was performed, and 1 mL of octafluoropropace (C3F8) was injected into the vitreous cavity. Following the surgery, all patients were instructed to maintain a prone position for three days to promote optimal recovery and absorption of the injected solution. 2.3.2 Subretinal injection of BSS procedure A self-made subretinal injection device was used, consisting of a 1 mL injection syringe, a set of Alcon® viscoelastic material control tubes, a Medone ® 38 gauge microinjection needle, and a 3 cm reusable silicone sleeve. Another 1 mL syringe was used to extract BSS and transfer it to the empty barrel of the device’s 1 mL syringe. The device was connected to a vitreous cutter silicone oil injection control unit and subjected to vacuum suction. Intraoperative OCT (iOCT; Zeiss RESCAN 700 OCT System, Germany) was used for real-time guidance. Constant pressure (maintained at a controlled level of 6 psi) was applied using a foot pedal to the plunger of the 1 mL syringe, allowing controlled injection up to 0.05 mL of BSS into the subretinal space (Fig. 1 and Video 1, which demonstrates the surgical procedure and iOCT for subretinal injection). 2.3.3 Intravitreal injection procedure The patients were treated with intravitreal injection of anti-VEGF when the edema remained or recurred. Under surface anesthesia, drug injection was performed at the 11 o 'clock position of the operative eye. After operation, the injection point was massaged with a cotton swab, and the patients were in free position. 2.4 Data Collection All participants were assessed prior to treatment, including the best corrected visual acuity (BCVA) assessment, intraocular pressure (IOP) measurement, slit-lamp microscopy, and spectral domain optical coherence tomography (SD-OCT). BCVA was evaluated using the international standard visual acuity chart, and the results were converted to the logarithm of the minimum resolution Angle (logMAR) visual acuity. A manual conversion was performed to convert Snellen visual acuity to 2.3 logMAR and counting fingers to 2.0 logMAR. Central macular thickness (CMT) were measured using an SD-OCT device (Topcon Triton, Japan). Slit-lamp and OCT examinations were performed in both groups during follow-up. BCVA, IOP and adverse complications were recorded. Recurrence as well as retreatment maintenance were collected. 2.5 Statistical Analysis Statistical analysis was performed with SPSS 26.0 (SPSS. Inc, USA). A normality test was used for all variables. Data are expressed as mean ± SD with a normal distribution and moderate (interquartile range) otherwise. Parametric tests were used to compare normally distributed data, while non-normally distributed data were compared using non-parametric tests. The paired t-test and the Wilcoxon signed-rank test were applied to evaluate changes in OCT and BCVA in the same group. Independent samples t-test and the Mann–Whitney test were used to compare baseline data and treatment effects between the two groups. Chi-square test was performed for recurrence conditions. P < 0.05 was considered statistically significant. 3. Result 3.1 Baseline Information The baseline characteristics of the two groups are shown in Table 1 . The mean age was 67.33 ± 7.12 in the injection group and 67.1 ± 10.90 in the surgery group (P = 0.967). There were two patients with diabetes in the injection group and three in the surgery group, and the mean duration of diabetes was 7.5 ± 2.54 and 12.00 ± 15.62, respectively (P = 0.673). Although these patients had diabetes, retinal changes associated with diabetes were not found. There were six and seven patients with hypertension in the two groups, and the mean duration of hypertension was 12.17 ± 15.33 and 9.87 ± 8.15, respectively (P = 0.735). The two groups were comparable at baseline (Table 1 ). Table 1 Baseline characteristics of the two groups Surgery Group Injection group P value Number 10 9 Age(years) 67.1 ± 10.90 67.33 ± 7.12 0.967 Gentle(male/female) 2\8 4\5 0.350 Eye(right/left) 6\4 5\4 1.000 DM Yes (%) 3(30.00) 2(22.22) 1.000 DM duration (years) 12.00 ± 15.62 7.5 ± 2.54 0.673 HBP Yes (%) 7(70.00) 6(66.67) 1.000 HBP duration (years) 9.87 ± 8.15 12.17 ± 15.33 0.735 Notes: DM: Diabetes mellitus; HBP: High blood pressure. 3.2 Vision Outcomes Before the intervention, BCVA in the surgery group was 1.06 ± 0.31, which was significantly worse than that in the injection group (0.60 ± 0.28, P = 0.004). After the intervention, the BCVA of the surgery group improved (0.60 ± 0.45, P = 0.006), and the best visual acuity reached the same level as that of the injection group (0.53 ± 0.49, P = 0.622). The degree of visual acuity improvement in the surgery group was better than that in the injection group (0.45 ± 0.40, 0.06 ± 0.27, P = 0.025, Table 2 ). Table 2 Comparison of BCVA between the two groups Surgery Group Injection group Z/t P value BCVA before Intervention 1.06 ± 0.31 0.60 ± 0.28 3.387 b 0.004** Best BCVA after the intervention 0.60 ± 0.45 0.53 ± 0.49 0.493 a 0.622 ΔBCVA 0.45 ± 0.40 0.06 ± 0.27 2.460 b 0.025* Z/t 3.615 b 1.404 a P value 0.006** 0.160 Notes : BCVA: Best-corrected visual acuity (expressed as log MAR); ΔBCVA: Difference in BCVA before and after the intervention; a : Paired rank sum test; b : Paired t test. P -value: * P < 0.05, ** P < 0.01, *** P < 0.001. 3.3 Edema Outcomes Before the intervention, CMT in the surgical group was 512.50 ± 72.99 µm, which was thicker than that in the injection group (461.56 ± 154.60 µm, P = 0.363). The minimum CMT of the two groups after intervention was 266.40 ± 52.08 µm and 221.89 ± 38.62 µm (P = 0.051), respectively, and the degree was similar. Both groups showed significant CMT reduction and decreased edema compared to baseline (P < 0.001, P = 0.008). The difference of CMT before and after treatment in the two groups was 246.10 ± 93.96 µm and 226.11 ± 155.75µm (P = 0.736), respectively, with the same level (Table 3 ). Table 3 Comparison of CMT between the two groups Surgery Group Injection group t P value CMT before Intervention(µm) 512.50 ± 72.99 461.56 ± 154.60 0.935 b 0.363 Minimum CMT during the follow-up(µm) 266.40 ± 52.08 221.89 ± 38.62 2.095 b 0.051 ΔCMT thickness(µm) 246.10 ± 93.96 226.11 ± 155.75 0.343 b 0.736 Z/t 8.283 b 2.666 a P value <0.001*** 0.008** Notes : CMT: Central macular thickness; ΔCMT: Difference in CMT before and after the intervention. a : Paired rank sum test; b : Paired t test. P -value: * P < 0.05, ** P < 0.01, *** P < 0.001. 3.4 Edema Recurrence Condition After intervention, the recurrence rate of the surgery group was 40%, which was lower than that of the injection group (88.9%, P = 0.051). The number of recurrences in the surgery group was less than that in the injection group (P = 0.61). At recurrence, CMT increased by 195.50 ± 27.86 µm and 290.00 ± 182.61 µm (P = 0.192) in both groups. The CMT values achieved were 473.00 ± 45.44 µm and 586.89 ± 169.18 µm (P = 0.225) at recurrence, respectively (Table 4 ). Thickening was lower in the surgery group. Figure 1 shows the full treatment–recurrence–retreatment course of a representative patient from the surgery group. Table 4 Recurrence of edema in the two groups Surgery Group Injection group P value Recurrence(%) Recurrence 4(40.0) 8(88.9) 0.051 No recurrence 6(60.0) 1(11.1) Number of recurrences 1(1, 1.75) 1(1, 4) 0.61 Maximum recurrence CMT(µm) 473.00 ± 45.44 586.89 ± 169.18 0.225 ΔCMT of recurrences(µm) 195.50 ± 27.86 290.00 ± 182.61 0.192 Notes : CMT: Central macular thickness; ΔCMT: Differences in CMT before and after edema recurrence. 4. Discussion This is a retrospective study. This study compared the efficacy of surgical and injection treatments for patients with persistent or recurrent edema who had previously received intravitreal injection treatment for RVO-ME. The surgery group was treated with subretinal BSS injection after vitrectomy and ILM peeling. This procedure has not been used in the treatment of RVO-ME in previous studies. We aimed to compare the effectiveness of this procedure with medical therapy in improving visual acuity, resolving edema, and recurrence. In previous studies, 14 – 17 vitrectomy with or without ILM peeling for the treatment of RVO-ME has improved visual acuity compared with that before surgery, with clear long-term effects. These findings are similar to our results. In the clinic, repeated anti-VEGF therapy is necessary to maintain long-term visual stability and prevent visual loss in patients with RVO-ME. 18 In our study, the visual improvement of patients with injection therapy was limited and did not achieve the dramatic effect of surgery. In terms of the long-term treatment of RVO-ME, the visual efficacy of anti-VEGF therapy in patients with recurrent edema was reduced. 18 – 20 This may be related to the damage of the retinal structure caused by repeated edema. Second, related to the ceiling effect, patients with poor baseline visual acuity had a better treatment effect than those with better baseline visual acuity. In our study, vitrectomy combined with internal limiting membrane peeling and subretinal injection of BSS was effective for ME. In our follow-up records, edema resolution was mostly observed at 1 week after surgery. Other studies have mentioned that the possible mechanisms of PPV combined with ILM peeling to improve RVO-ME included the release of traction, removal of angiogenic agents, and improvement of retinal oxygenation. 15 , 21 In addition, based on the previous application of subretinal BSS injection in DME and severe idiopathic epiretinal membranes, 13 , 22 we hypothesized that this treatment could dilute the accumulation of inflammatory factors in the retina, increase retinal oxygenation, and promote circulation, thereby improving persistent edema. In our study, the injection site was chosen based on the 2–3 optic disk diameters from the macula to reduce unnecessary mechanical damage to the macula and ensure that BSS played a therapeutic role in ME. In terms of recurrence, surgical treatment showed advantages in recurrence rate and number. RVO-ME may be a chronic and long-term condition, and patients with this condition present with recurrent edema that requires long-term repeated anti-VEGF injection therapy for maintenance. 23 The mean number of ranibizumab injections up to month 12 is 8.1. 24 Half equire at least three injections annually thereafter, and some still need up to six injections in the fourth year. 18 If the injection frequency is not sufficient according to the treatment plan, the therapeutic effect is difficult to guarantee. Under pro re nata regimens, an insufficient number of follow-up visits can delay detection of recurrent edema, increasing the risk of undertreatment and subsequent neovascularization. 25 The macula undergoes repeated relapses of edema, which damage the photoreceptors. Previous studies have found that significant improvement in retinal thickness is not accompanied by a significant increase in BCVA, and there is no simple linear relationship between retinal thickness and visual acuity. 25 , 26 This aligns with our findings: while edema in the injection group resolved after retreatment, visual acuity did not improve significantly. In contrast, the surgery group demonstrated a more stable treatment effect. In addition, our study showed that CMT was lower in the surgery group compared with that in the injection group in patients with recurrence. This may be related to the dilution of inflammatory factors by BSS as well as the aforementioned improvement in oxygenation. which helps disrupt the vicious cycle that contributes to chronic ME. 13 Surgical intervention thus appears to reduce both the frequency and severity of edema recurrence, providing visual and anatomical benefits, improving quality of life, and reducing the burden of repeated treatment. The safety of subretinal injection of BSS has been confirmed in many studies. In clinical applications the injection can be ensured by controlling the injection dose and pressure using methods similar to our self-made injection device. With the updating of equipment, such as iOCT, the operation of subretinal injections can be visualized. It can assist surgeons with observing the macular area morphology during the injection. The retina bulges rapidly during the injection and the surgeon can judge timely whether there is an iatrogenic macular hole due to pressure on the retina. In our study, no macular hole formation was observed. In addition, the depth of the needle can be observed using iOCT to avoid damage to the RPE, which affects retinal function. All the above ensure that the technique of subretinal BSS injections can be safely performed during surgery. In summary, vitrectomy combined with internal limiting membrane peeling and subretinal BSS injection was effective and safe for patients with RVO with persistent or recurrent edema in our study. It provides advantages in improving visual acuity and maintaining retinal morphology. This study compared first-line anti-VEGF therapy as a control group and demonstrated that surgery can achieve the same or even better treatment results. A possible limitation is that this study was retrospective and therefore had limited clinical data. 5. Conclusions In our study, vitrectomy combined with internal limiting membrane peeling and subretinal BSS injection was effective and safe for patients with RVO with persistent or recurrent edema.Vitrectomy combined with internal limiting membrane peeling and subretinal BSS injection improves the visual acuity of patients with RVO-ME, reduces edema, and lowers recurrence. Abbreviations anti-VEGF anti-vascular endothelial growth factor BCVA Best corrected visual acuity BSS Balanced salt solution CMT Central macular thickness DME Diabetic macular edema DM Diabetes mellitus; HBP High blood pressure ILM Internal limiting membrane IOP Intraocular pressure ME Macular edema RPE Retinal pigment epithelium RVO Retinal vein occlusion RVO-ME Macular edema secondary to retinal vein occlusion Declarations Ethics approval and consent to participate This study was conducted in accordance with the principles of the Declaration of Helsinki. Informed consent was obtained from all the patients and was approved by the Clinical Trials Ethics Committee of Tianjin Medical University Eye Hospital (2025KY-03). Availability of data and materials All data generated or analysed during this study are included in this published article Competing interests The authors declare no conflicts of interest or financial relationships that could influence this research. Funding 1.Tianjin Binhai New Area Health Commission Project (No. 2023BWKZ006). 2.Tianjin Key Medical Discipline (Specialty) Construction Project (TJYXZDXK-037A). 3.The Science&Technology Development Fund of Tianjin Education Commission for Higher Education (No.2022ZD058). Authors' contributions Conception and design of study: Yue Pan, Xiang Zhang, and Bojie Hu. Clinical guidance and surgical implementation: Wenbo Li, Xiaorong Li and Bojie Hu. Acquisition and statistical analysis of data: Yue Pan, Jiaxing Chi, Chang Liu and Mengqi An. Interpretation of data: Yue Pan, Xiang Zhang, Qinning Xie and Zetong Nie. Drafting and critical revision: Yue Pan, Xiang Zhang, Wenbo Li and Bojie Hu. Supervision: Wenbo Li and Bojie Hu. References Rogers S, McIntosh RL, Cheung N, et al. The Prevalence of Retinal Vein Occlusion: Pooled Data from Population Studies from the United States, Europe, Asia, and Australia. Ophthalmology . 2010;117(2):313. doi:10.1016/j.ophtha.2009.07.017 Ascaso FJ, Huerva V, Grzybowski A. The Role of Inflammation in the Pathogenesis of Macular Edema Secondary to Retinal Vascular Diseases. Mediators Inflamm . 2014;2014:432685. doi:10.1155/2014/432685 Tadayoni R, Waldstein SM, Boscia F, et al. Sustained Benefits of Ranibizumab with or without Laser in Branch Retinal Vein Occlusion: 24-Month Results of the BRIGHTER Study. Ophthalmology . 2017;124(12):1778-1787. doi:10.1016/j.ophtha.2017.06.027 Yoon YH, Kim JW, Lee JY, et al. Dexamethasone Intravitreal Implant for Early Treatment and Retreatment of Macular Edema Related to Branch Retinal Vein Occlusion: The Multicenter COBALT Study. Ophthalmologica . 2018;240(2):81-89. doi:10.1159/000487547 Giuffrè C, Cicinelli MV, Marchese A, Coppola M, Parodi MB, Bandello F. Simultaneous intravitreal dexamethasone and aflibercept for refractory macular edema secondary to retinal vein occlusion. Graefes Arch Clin Exp Ophthalmol . 2020;258(4):787-793. doi:10.1007/s00417-019-04577-8 Namvar E, Yasemi M, Nowroozzadeh MH, Ahmadieh H. Intravitreal Injection of Anti-Vascular Endothelial Growth Factors Combined with Corticosteroids for the Treatment of Macular Edema Secondary to Retinal Vein Occlusion: A Systematic Review and Meta-Analysis. Semin Ophthalmol . 2024;39(1):109-119. doi:10.1080/08820538.2023.2249527 Yamada H, Imai H, Tetsumoto A, et al. Cystotomy with or without fibrinogen clot removal for refractory cystoid macular edema secondary to branch retinal vein occlusion. Sci Rep . 2021;11:8460. doi:10.1038/s41598-021-88149-z Yuan Q, Gao Y, Liu Y, Xu H, Wang T, Zhang M. Efficacy of single-dose intravitreal dexamethasone implantation for retinal vein occlusion patients with refractory macular edema: A systematic review and meta-analysis. Front Pharmacol . 2022;13:951666. doi:10.3389/fphar.2022.951666 Zhang L, Huang Y, Chen J, Xu X, Xu F, Yao J. Multimodal deep transfer learning to predict retinal vein occlusion macular edema recurrence after anti-VEGF therapy. Heliyon. 2024 Apr 10;10(8):e29334. doi: 10.1016/j.heliyon.2024.e29334. Kumagai K, Ogino N, Fukami M, Furukawa M. Removal of foveal hard exudates by subretinal balanced salt solution injection using 38-gauge needle in diabetic patients. Graefes Arch Clin Exp Ophthalmol . 2020;258(9):1893-1899. doi:10.1007/s00417-020-04756-y Handa S, Dogra M, Tigari B, Katoch D, Singh R. Displacement of submacular hemorrhage with vitrectomy combined with subretinal balanced salt solution and air. Retina . Published online July 21, 2023. doi:10.1097/IAE.0000000000003879 Saab M, Javidi S, Dirani A, et al. Displacement of Retained Subretinal Perfluorocarbon Liquid Through Therapeutic Retinal Detachment Induced by Balanced Salt Solution Injection. Int Med Case Rep J. 2020;13:183-186. https://doi.org/10.2147/IMCRJ.S244166 Mao Z, You Z. Internal Limiting Peeling in Conjunction with Subretinal Injection of a Balanced Salt Solution in the Macular Region to Treat Refractory Diabetic Macular Edema. Altern Ther Health Med. 2024 Apr 18:AT10722. Epub ahead of print. Kumagai K, Ogino N, Fukami M, et al. Long-term outcomes of intravitreous bevacizumab or tissue plasminogen activator or vitrectomy for macular edema due to branch retinal vein occlusion. Clin Ophthalmol. 2019;13:617-626. https://doi.org/10.2147/OPTH.S195600 Kumagai K, Ogino N, Fukami M, et al. Vitrectomy for macular edema due to retinal vein occlusion. Clin Ophthalmol. 2019;13:969-984. https://doi.org/10.2147/OPTH.S203212 Park DH, Kim IT. Long-term effects of vitrectomy and internal limiting membrane peeling for macular edema secondary to central retinal vein occlusion and hemiretinal vein occlusion. Retina Phila Pa . 2010;30(1):117-124. doi:10.1097/IAE.0b013e3181bced68 Baharivand N, Hariri A, Javadzadeh A, Heidari E, Sadegi K. Pars plana vitrectomy and internal limiting membrane peeling for macular edema secondary to retinal vein occlusion. Clin Ophthalmol. 2011;5:1089-93. doi: 10.2147/OPTH.S23164. Campochiaro PA, Sophie R, Pearlman J, et al. Long-term Outcomes in Patients with Retinal Vein Occlusion Treated with Ranibizumab: The RETAIN Study. Ophthalmology . 2014;121(1):209-219. doi:10.1016/j.ophtha.2013.08.038 Iftikhar M, Mir TA, Hafiz G, et al. Loss of Peak Vision in Retinal Vein Occlusion Patients Treated for Macular Edema. Am J Ophthalmol . 2019;205:17-26. doi:10.1016/j.ajo.2019.03.029 Larsen M, Waldstein SM, Boscia F, et al. Individualized Ranibizumab Regimen Driven by Stabilization Criteria for Central Retinal Vein Occlusion: Twelve-Month Results of the CRYSTAL Study. Ophthalmology . 2016;123(5):1101-1111. doi:10.1016/j.ophtha.2016.01.011 Nishida A, Kojima H, Kameda T, Mandai M, Kurimoto Y. Five-year outcomes of pars plana vitrectomy for macular edema associated with branch retinal vein occlusion. Clin Ophthalmol . 2017;11:369-375. doi:10.2147/OPTH.S123419 Luan R, Liu B, Cai B, Gong Y, Li X. Application of Subretinal Balanced Salt Solution Injection: A Novel technique in treating Severe idiopathic Epiretinal Membrane. RETINA . Published online May 12, 2022:10.1097/IAE.0000000000004282. doi:10.1097/IAE.0000000000004282 Ip M, Modi Y, Fekrat S, Gibson K, Boucher N, Arrisi P, Ishii F, Liu Y, Paris LP, Fenech M, Chi GC. Treatment Patterns and Long-Term Outcomes with Anti-VEGF Therapy for Retinal Vein Occlusion: An Analysis of the Vestrum Database. Ophthalmol Retina. 2025 May 27:S2468-6530(25)00251-9. doi: 10.1016/j.oret.2025.05.025. Larsen M, Waldstein SM, Boscia F, et al. Individualized Ranibizumab Regimen Driven by Stabilization Criteria for Central Retinal Vein Occlusion: Twelve-Month Results of the CRYSTAL Study. Ophthalmology. 2016;123(5):1101-1111. https://doi.org/10.1016/j.ophtha.2016.01.011. Hamam M, Lagali N, Abdulnour E, Setterud H, Johansson B, Mirabelli P. Real-Life Efficacy of Bevacizumab Treatment for Macular Edema Secondary to Central Retinal Vein Occlusion according to Pro Re Nata or Treat-and-Extend Regimen in Eyes with or without Epiretinal Membrane. J Ophthalmol . 2022;2022:6288582. doi:10.1155/2022/6288582 Scott IU, Oden NL, VanVeldhuisen PC, Ip MS, Blodi BA; SCORE2 Investigator Group. SCORE2 Report 24: Nonlinear Relationship of Retinal Thickness and Visual Acuity in Central Retinal and Hemiretinal Vein Occlusion. Ophthalmology. 2023 Oct;130(10):1066-1072. doi: 10.1016/j.ophtha.2023.05.023. Additional Declarations No competing interests reported. Supplementary Files video1.mp4 Supplemental Digital Content 1.mp4 Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-7385007","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":504989500,"identity":"5b94cb2b-3499-4217-8f2e-21b6bddc7d44","order_by":0,"name":"Yue Pan","email":"","orcid":"","institution":"Tianjin Medical University Eye Hospital","correspondingAuthor":false,"prefix":"","firstName":"Yue","middleName":"","lastName":"Pan","suffix":""},{"id":504989502,"identity":"18edbcf8-1c4a-48e9-9ade-034fb279a7d2","order_by":1,"name":"Xiang Zhang","email":"","orcid":"","institution":"Tianjin Medical University Eye Hospital","correspondingAuthor":false,"prefix":"","firstName":"Xiang","middleName":"","lastName":"Zhang","suffix":""},{"id":504989504,"identity":"697f63f0-8f21-4aa1-bc14-10a395ede599","order_by":2,"name":"Zetong Nie","email":"","orcid":"","institution":"Tianjin Medical University Eye Hospital","correspondingAuthor":false,"prefix":"","firstName":"Zetong","middleName":"","lastName":"Nie","suffix":""},{"id":504989505,"identity":"4b6a3ad2-9790-455b-8284-fb90317a338f","order_by":3,"name":"Jiaxing Chi","email":"","orcid":"","institution":"Tianjin Medical University Eye Hospital","correspondingAuthor":false,"prefix":"","firstName":"Jiaxing","middleName":"","lastName":"Chi","suffix":""},{"id":504989506,"identity":"c885363b-d28b-4035-b6d3-27b464ab6657","order_by":4,"name":"Chang Liu","email":"","orcid":"","institution":"Tianjin Medical University Eye Hospital","correspondingAuthor":false,"prefix":"","firstName":"Chang","middleName":"","lastName":"Liu","suffix":""},{"id":504989507,"identity":"46a6aadb-d8a1-4f63-a20f-cbe3d7acaa45","order_by":5,"name":"Qinning Xie","email":"","orcid":"","institution":"Tianjin Medical University Eye Hospital","correspondingAuthor":false,"prefix":"","firstName":"Qinning","middleName":"","lastName":"Xie","suffix":""},{"id":504989508,"identity":"f5faaaa5-2590-446d-96be-989311e425a6","order_by":6,"name":"Mengqi An","email":"","orcid":"","institution":"Tianjin Medical University Eye Hospital","correspondingAuthor":false,"prefix":"","firstName":"Mengqi","middleName":"","lastName":"An","suffix":""},{"id":504989509,"identity":"76bd83c1-9e8f-4680-bf04-f67e39053cc8","order_by":7,"name":"Xiaorong Li","email":"","orcid":"","institution":"Tianjin Medical University Eye Hospital","correspondingAuthor":false,"prefix":"","firstName":"Xiaorong","middleName":"","lastName":"Li","suffix":""},{"id":504989510,"identity":"df747e2b-393d-4a8d-a7fc-4b099e406013","order_by":8,"name":"Wenbo Li","email":"","orcid":"","institution":"Tianjin Medical University Eye Hospital","correspondingAuthor":false,"prefix":"","firstName":"Wenbo","middleName":"","lastName":"Li","suffix":""},{"id":504989511,"identity":"423117fb-1efc-429f-bb40-b4e581a89603","order_by":9,"name":"Bojie Hu","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAsElEQVRIiWNgGAWjYBACAwkGhsN/KiAcCWK1MD7gOWNAmhZmA942UrSYS/eYSUjO+xNtcID54G0eBrs8glos55wxkzDcZpC74QBbsjUPQ3IxYYfdyDGTSARr4TGT5mE4kNhAlJaDc0Ba+L8RrcXYsLEBbAsbcVosZ6QVPmY4Zpw78zCbseUcg2TCWswlkjccZqiRy+073vzwxpsKO8JaEIAZ7E7i1Y+CUTAKRsEowAMAWHE6DCHDfo8AAAAASUVORK5CYII=","orcid":"","institution":"Tianjin Medical University Chu Hsien-I Memorial Hospital","correspondingAuthor":true,"prefix":"","firstName":"Bojie","middleName":"","lastName":"Hu","suffix":""}],"badges":[],"createdAt":"2025-08-16 04:38:15","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-7385007/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-7385007/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":90306954,"identity":"3c77b9ad-93eb-4ec6-a998-d80cd0c81b84","added_by":"auto","created_at":"2025-09-01 09:29:03","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":254423,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eIntraoperative and postoperative images of one case in surgery group\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003ea: The fundus as seen in an intraoperative video and the area scanned by iOCT. b: iOCT images of the corresponding regions before subretinal injection. c: iOCT images of the corresponding regions after subretinal injection. The macular area was elevated, and no macular hole was observed. d: Preoperative OCT images. e: OCT images one week after surgery. f: OCT images six months after surgery. g: Cataract and recurrent ME were found during follow-up, and cataract surgery and anti-VEGF drug treatment were performed. h: OCT images two months after cataract surgery and retreatment. ME resolved and the patient’s log MAR BCVA returned to 0.3.\u003c/p\u003e","description":"","filename":"Figure1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-7385007/v1/3fb81b69fc79db3cd8c1d409.jpg"},{"id":90750537,"identity":"f105892d-f8cd-47aa-ade3-be3930dd6ef7","added_by":"auto","created_at":"2025-09-07 10:01:46","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1213382,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7385007/v1/88424fcb-7981-4c97-b006-8e17394c1271.pdf"},{"id":90306963,"identity":"0103229c-cc75-4b76-a19a-e101bbb9d2da","added_by":"auto","created_at":"2025-09-01 09:29:07","extension":"mp4","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":101114033,"visible":true,"origin":"","legend":"\u003cp\u003eSupplemental Digital Content 1.mp4\u003c/p\u003e","description":"","filename":"video1.mp4","url":"https://assets-eu.researchsquare.com/files/rs-7385007/v1/677ed2a1942a8bda3b047568.mp4"}],"financialInterests":"No competing interests reported.","formattedTitle":"Subretinal Injection of Balanced Salt Solution for Macular Edema Secondary to Retinal Vein Occlusion","fulltext":[{"header":"1. Introduction","content":"\u003cp\u003eRetinal vein occlusion (RVO) is the second most common disease in vitreoretinopathy after diabetic retinopathy, and macular edema (ME) is the most common RVO complication, leading to visual impairment.\u003csup\u003e\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u003c/sup\u003e The pathogenesis of macular edema secondary to retinal vein occlusion (RVO-ME) remains unclear and is mainly related to destruction of the inner blood\u0026ndash;retinal barrier, high vascular permeability, and increased local inflammatory response.\u003csup\u003e\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u003c/sup\u003e Clinically, the preferred treatment for RVO-ME is intravitreal injection of anti-vascular endothelial growth factor (anti-VEGF) drugs, which have shown long-term therapeutic effects in restoring visual function and macular morphology.\u003csup\u003e\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u003c/sup\u003e However, it has been observed in clinic and in some studies that the efficacy of anti-VEGF drug in ME treatment is limited in some patients, and the mechanism underlying this condition is complex. Notably, Ozurdex improves initial and refractory ME.\u003csup\u003e\u003cspan additionalcitationids=\"CR5\" citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u003c/sup\u003e Additional approaches such as cyst resection, combination therapy with Ozurdex and anti-VEGF agents, and subthreshold micropulse laser treatment have also been used for refractory ME.\u003csup\u003e\u003cspan additionalcitationids=\"CR8\" citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u003c/sup\u003e RVO-ME has been a very challenging issue for clinicians because it can lead to irreversible vision loss if not followed up and managed promptly, and some patients respond poorly to anti-VEGF therapy or experience recurrence after improvement.\u003c/p\u003e\u003cp\u003eSubretinal injection of a balanced salt solution (BSS) is a novel clinical technique which has been applied in some clinical studies, and its safety and effectiveness have been confirmed.\u003csup\u003e\u003cspan additionalcitationids=\"CR11\" citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e\u003c/sup\u003e Mao et al. used this technique to treat refractory diabetic macular edema (DME) and found that DME resolved significantly at 1 week and 1 month after surgery.\u003csup\u003e\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e\u003c/sup\u003eSubretinal BSS injection may reduce the colloid osmotic pressure in the retinal tissue, remove inflammatory factors and migrating cells from the retinal pigment epithelium (RPE), and reduce the production and accumulation of inflammatory factors, thus improving persistent or recurrent edema To date, no studies have specifically examined subretinal BSS injection for RVO-ME. Considering the recurrent edema of RVO-ME and the burden of continuous injection, we considered whether surgery could achieve edema resolution, visual improvement, and long-term maintenance.\u003c/p\u003e\u003cp\u003eIn this study, we investigated the efficacy of vitrectomy combined with subretinal injection of BSS compared with injection in the treatment of recurrent RVO-ME for edema resolution, visual improvement, and recurrence of edema.\u003c/p\u003e"},{"header":"2. Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\u003ch2\u003e2.1 Study Design\u003c/h2\u003e\u003cp\u003eThis retrospective study was conducted at Tianjin Medical University Eye Hospital. Patients with RVO-ME were enrolled from June 2023 through December 2024. This study was conducted in accordance with the principles of the Declaration of Helsinki and was approved by the Clinical Trials Ethics Committee of Tianjin Medical University Eye Hospital (2025KY-03).\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec4\" class=\"Section2\"\u003e\u003ch2\u003e2.2 Study Population\u003c/h2\u003e\u003cp\u003eA total of 19 eyes from 19 patients were included in this study, characterized by a diagnosis of RVO on retinal angiography, confirmed presence of ME on OCT images, and persistent or recurrent edema after at least three standard doses of anti-VEGF therapy. Patients with coexisting ocular conditions (age-related macular degeneration, retinal detachment, or diabetic retinopathy) were excluded. Of the 19 patients, 10 underwent surgery and 9 underwent intravitreal injections. The surgery group underwent vitrectomy combined with internal limiting membrane (ILM) peeling and subretinal injection of BSS. The injection group continued to receive anti-VEGF therapy.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec5\" class=\"Section2\"\u003e\u003ch2\u003e2.3 Clinical Study Protocol\u003c/h2\u003e\u003cdiv id=\"Sec6\" class=\"Section3\"\u003e\u003ch2\u003e2.3.1 Surgical procedure\u003c/h2\u003e\u003cp\u003eAll patients of surgery group underwent surgical procedures performed by the same experienced surgeon. If the patient had significant opacification, phacoemulsification and intraocular lens implantation were performed. The surgical procedure was conducted using an OPMI LUMERA T surgical microscope. The main surgical procedure was as follows:\u003c/p\u003e\u003cp\u003eA 25 gauge minimally invasive pars plana vitrectomy (PPV) was performed using the CONSTELLATION vitrectomy system, and complete posterior vitreous detachment was done with triamcinolone acetonide assistance. ILM approximately three optic disc diameters were peeling with the assistance of 0.025% indocyanine green staining. Subretinal injection of BSS was performed (see 2. Subretinal Injection of BSS procedure). Air-liquid exchange was performed, and 1 mL of octafluoropropace (C3F8) was injected into the vitreous cavity. Following the surgery, all patients were instructed to maintain a prone position for three days to promote optimal recovery and absorption of the injected solution.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec7\" class=\"Section3\"\u003e\u003ch2\u003e2.3.2 Subretinal injection of BSS procedure\u003c/h2\u003e\u003cp\u003eA self-made subretinal injection device was used, consisting of a 1 mL injection syringe, a set of Alcon\u0026reg; viscoelastic material control tubes, a Medone \u0026reg; 38 gauge microinjection needle, and a 3 cm reusable silicone sleeve. Another 1 mL syringe was used to extract BSS and transfer it to the empty barrel of the device\u0026rsquo;s 1 mL syringe. The device was connected to a vitreous cutter silicone oil injection control unit and subjected to vacuum suction.\u003c/p\u003e\u003cp\u003eIntraoperative OCT (iOCT; Zeiss RESCAN 700 OCT System, Germany) was used for real-time guidance. Constant pressure (maintained at a controlled level of 6 psi) was applied using a foot pedal to the plunger of the 1 mL syringe, allowing controlled injection up to 0.05 mL of BSS into the subretinal space (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e and Video 1, which demonstrates the surgical procedure and iOCT for subretinal injection).\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec8\" class=\"Section3\"\u003e\u003ch2\u003e2.3.3 Intravitreal injection procedure\u003c/h2\u003e\u003cp\u003eThe patients were treated with intravitreal injection of anti-VEGF when the edema remained or recurred. Under surface anesthesia, drug injection was performed at the 11 o 'clock position of the operative eye. After operation, the injection point was massaged with a cotton swab, and the patients were in free position.\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv id=\"Sec9\" class=\"Section2\"\u003e\u003ch2\u003e2.4 Data Collection\u003c/h2\u003e\u003cp\u003eAll participants were assessed prior to treatment, including the best corrected visual acuity (BCVA) assessment, intraocular pressure (IOP) measurement, slit-lamp microscopy, and spectral domain optical coherence tomography (SD-OCT). BCVA was evaluated using the international standard visual acuity chart, and the results were converted to the logarithm of the minimum resolution Angle (logMAR) visual acuity. A manual conversion was performed to convert Snellen visual acuity to 2.3 logMAR and counting fingers to 2.0 logMAR. Central macular thickness (CMT) were measured using an SD-OCT device (Topcon Triton, Japan).\u003c/p\u003e\u003cp\u003eSlit-lamp and OCT examinations were performed in both groups during follow-up. BCVA, IOP and adverse complications were recorded. Recurrence as well as retreatment maintenance were collected.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec10\" class=\"Section2\"\u003e\u003ch2\u003e2.5 Statistical Analysis\u003c/h2\u003e\u003cp\u003eStatistical analysis was performed with SPSS 26.0 (SPSS. Inc, USA). A normality test was used for all variables. Data are expressed as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD with a normal distribution and moderate (interquartile range) otherwise. Parametric tests were used to compare normally distributed data, while non-normally distributed data were compared using non-parametric tests. The paired t-test and the Wilcoxon signed-rank test were applied to evaluate changes in OCT and BCVA in the same group. Independent samples t-test and the Mann\u0026ndash;Whitney test were used to compare baseline data and treatment effects between the two groups. Chi-square test was performed for recurrence conditions. P\u0026thinsp;\u0026lt;\u0026thinsp;0.05 was considered statistically significant.\u003c/p\u003e\u003c/div\u003e"},{"header":"3. Result","content":"\u003cdiv id=\"Sec12\" class=\"Section2\"\u003e\u003ch2\u003e3.1 Baseline Information\u003c/h2\u003e\u003cp\u003eThe baseline characteristics of the two groups are shown in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. The mean age was 67.33\u0026thinsp;\u0026plusmn;\u0026thinsp;7.12 in the injection group and 67.1\u0026thinsp;\u0026plusmn;\u0026thinsp;10.90 in the surgery group (P\u0026thinsp;=\u0026thinsp;0.967). There were two patients with diabetes in the injection group and three in the surgery group, and the mean duration of diabetes was 7.5\u0026thinsp;\u0026plusmn;\u0026thinsp;2.54 and 12.00\u0026thinsp;\u0026plusmn;\u0026thinsp;15.62, respectively (P\u0026thinsp;=\u0026thinsp;0.673). Although these patients had diabetes, retinal changes associated with diabetes were not found. There were six and seven patients with hypertension in the two groups, and the mean duration of hypertension was 12.17\u0026thinsp;\u0026plusmn;\u0026thinsp;15.33 and 9.87\u0026thinsp;\u0026plusmn;\u0026thinsp;8.15, respectively (P\u0026thinsp;=\u0026thinsp;0.735). The two groups were comparable at baseline (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\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\u003e\u003cb\u003eBaseline characteristics of the two groups\u003c/b\u003e\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\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eSurgery Group\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eInjection group\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cem\u003eP\u003c/em\u003e value\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eNumber\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e10\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eAge(years)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e67.1\u0026thinsp;\u0026plusmn;\u0026thinsp;10.90\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e67.33\u0026thinsp;\u0026plusmn;\u0026thinsp;7.12\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.967\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eGentle(male/female)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2\\8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e4\\5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.350\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eEye(right/left)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e6\\4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e5\\4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e1.000\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eDM\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eYes (%)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e3(30.00)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e2(22.22)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e1.000\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eDM duration (years)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e12.00\u0026thinsp;\u0026plusmn;\u0026thinsp;15.62\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e7.5\u0026thinsp;\u0026plusmn;\u0026thinsp;2.54\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.673\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eHBP\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eYes (%)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e7(70.00)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e6(66.67)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e1.000\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eHBP duration (years)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e9.87\u0026thinsp;\u0026plusmn;\u0026thinsp;8.15\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e12.17\u0026thinsp;\u0026plusmn;\u0026thinsp;15.33\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.735\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"4\"\u003eNotes: DM: Diabetes mellitus; HBP: High blood pressure.\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec13\" class=\"Section2\"\u003e\u003ch2\u003e3.2 Vision Outcomes\u003c/h2\u003e\u003cp\u003eBefore the intervention, BCVA in the surgery group was 1.06\u0026thinsp;\u0026plusmn;\u0026thinsp;0.31, which was significantly worse than that in the injection group (0.60\u0026thinsp;\u0026plusmn;\u0026thinsp;0.28, P\u0026thinsp;=\u0026thinsp;0.004). After the intervention, the BCVA of the surgery group improved (0.60\u0026thinsp;\u0026plusmn;\u0026thinsp;0.45, P\u0026thinsp;=\u0026thinsp;0.006), and the best visual acuity reached the same level as that of the injection group (0.53\u0026thinsp;\u0026plusmn;\u0026thinsp;0.49, P\u0026thinsp;=\u0026thinsp;0.622). The degree of visual acuity improvement in the surgery group was better than that in the injection group (0.45\u0026thinsp;\u0026plusmn;\u0026thinsp;0.40, 0.06\u0026thinsp;\u0026plusmn;\u0026thinsp;0.27, P\u0026thinsp;=\u0026thinsp;0.025, Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003e\u003cb\u003eComparison of BCVA between the two groups \u003c/b\u003e\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=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\"\u0026plusmn;\" 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=\"char\" char=\".\" 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\u003eSurgery Group\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e\u003cp\u003eInjection group\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c6\"\u003e\u003cp\u003eZ/t\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c7\"\u003e\u003cp\u003e\u003cem\u003eP\u003c/em\u003e value\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eBCVA before Intervention\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1.06\u0026thinsp;\u0026plusmn;\u0026thinsp;0.31\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.60\u0026thinsp;\u0026plusmn;\u0026thinsp;0.28\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e3.387\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e0.004**\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eBest BCVA after the intervention\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.60\u0026thinsp;\u0026plusmn;\u0026thinsp;0.45\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.53\u0026thinsp;\u0026plusmn;\u0026thinsp;0.49\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.493\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e0.622\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eΔBCVA\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e\u003cp\u003e0.45\u0026thinsp;\u0026plusmn;\u0026thinsp;0.40\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c5\"\u003e\u003cp\u003e0.06\u0026thinsp;\u0026plusmn;\u0026thinsp;0.27\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e2.460\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e0.025*\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eZ/t\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e3.615\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e1.404\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eP\u003c/b\u003e \u003cb\u003evalue\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.006**\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.160\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003e\u003cb\u003eNotes\u003c/b\u003e: BCVA: Best-corrected visual acuity (expressed as log MAR); ΔBCVA: Difference in BCVA before and after the intervention; \u003csup\u003ea\u003c/sup\u003e: Paired rank sum test; \u003csup\u003eb\u003c/sup\u003e: Paired t test. \u003cem\u003eP\u003c/em\u003e-value: *\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05, **\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.01, ***\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec14\" class=\"Section2\"\u003e\u003ch2\u003e3.3 Edema Outcomes\u003c/h2\u003e\u003cp\u003eBefore the intervention, CMT in the surgical group was 512.50\u0026thinsp;\u0026plusmn;\u0026thinsp;72.99 \u0026micro;m, which was thicker than that in the injection group (461.56\u0026thinsp;\u0026plusmn;\u0026thinsp;154.60 \u0026micro;m, P\u0026thinsp;=\u0026thinsp;0.363). The minimum CMT of the two groups after intervention was 266.40\u0026thinsp;\u0026plusmn;\u0026thinsp;52.08 \u0026micro;m and 221.89\u0026thinsp;\u0026plusmn;\u0026thinsp;38.62 \u0026micro;m (P\u0026thinsp;=\u0026thinsp;0.051), respectively, and the degree was similar. Both groups showed significant CMT reduction and decreased edema compared to baseline (P\u0026thinsp;\u0026lt;\u0026thinsp;0.001, P\u0026thinsp;=\u0026thinsp;0.008). The difference of CMT before and after treatment in the two groups was 246.10\u0026thinsp;\u0026plusmn;\u0026thinsp;93.96 \u0026micro;m and 226.11\u0026thinsp;\u0026plusmn;\u0026thinsp;155.75\u0026micro;m (P\u0026thinsp;=\u0026thinsp;0.736), respectively, with the same level (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\u003eComparison of CMT between the two groups\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=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\"\u0026plusmn;\" 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=\"char\" char=\".\" 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\u003eSurgery Group\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e\u003cp\u003eInjection group\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c6\"\u003e\u003cp\u003et\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c7\"\u003e\u003cp\u003e\u003cem\u003eP\u003c/em\u003e value\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eCMT before Intervention(\u0026micro;m)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e512.50\u0026thinsp;\u0026plusmn;\u0026thinsp;72.99\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e461.56\u0026thinsp;\u0026plusmn;\u0026thinsp;154.60\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.935\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e0.363\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eMinimum CMT during the follow-up(\u0026micro;m)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e266.40\u0026thinsp;\u0026plusmn;\u0026thinsp;52.08\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e221.89\u0026thinsp;\u0026plusmn;\u0026thinsp;38.62\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e2.095\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e0.051\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eΔCMT thickness(\u0026micro;m)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e\u003cp\u003e246.10\u0026thinsp;\u0026plusmn;\u0026thinsp;93.96\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c5\"\u003e\u003cp\u003e226.11\u0026thinsp;\u0026plusmn;\u0026thinsp;155.75\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.343\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e0.736\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eZ/t\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e8.283\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e2.666\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eP\u003c/b\u003e \u003cb\u003evalue\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u0026lt;0.001***\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.008**\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"7\"\u003e\u003cb\u003eNotes\u003c/b\u003e: CMT: Central macular thickness; ΔCMT: Difference in CMT before and after the intervention. \u003csup\u003ea\u003c/sup\u003e: Paired rank sum test; \u003csup\u003eb\u003c/sup\u003e: Paired t test. \u003cem\u003eP\u003c/em\u003e-value: *\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05, **\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.01, ***\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001.\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec15\" class=\"Section2\"\u003e\u003ch2\u003e3.4 Edema Recurrence Condition\u003c/h2\u003e\u003cp\u003eAfter intervention, the recurrence rate of the surgery group was 40%, which was lower than that of the injection group (88.9%, P\u0026thinsp;=\u0026thinsp;0.051). The number of recurrences in the surgery group was less than that in the injection group (P\u0026thinsp;=\u0026thinsp;0.61). At recurrence, CMT increased by 195.50\u0026thinsp;\u0026plusmn;\u0026thinsp;27.86 \u0026micro;m and 290.00\u0026thinsp;\u0026plusmn;\u0026thinsp;182.61 \u0026micro;m (P\u0026thinsp;=\u0026thinsp;0.192) in both groups. The CMT values achieved were 473.00\u0026thinsp;\u0026plusmn;\u0026thinsp;45.44 \u0026micro;m and 586.89\u0026thinsp;\u0026plusmn;\u0026thinsp;169.18 \u0026micro;m (P\u0026thinsp;=\u0026thinsp;0.225) at recurrence, respectively (Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e). Thickening was lower in the surgery group. Figure\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e shows the full treatment\u0026ndash;recurrence\u0026ndash;retreatment course of a representative patient from the surgery group.\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\u003eRecurrence of edema in the two groups\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"4\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" 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\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eSurgery Group\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eInjection group\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cem\u003eP\u003c/em\u003e value\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eRecurrence(%)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eRecurrence\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e4(40.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e8(88.9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.051\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eNo recurrence\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e6(60.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1(11.1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eNumber of recurrences\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e1(1, 1.75)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1(1, 4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.61\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eMaximum recurrence CMT(\u0026micro;m)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e473.00\u0026thinsp;\u0026plusmn;\u0026thinsp;45.44\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e586.89\u0026thinsp;\u0026plusmn;\u0026thinsp;169.18\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.225\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eΔCMT of recurrences(\u0026micro;m)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e195.50\u0026thinsp;\u0026plusmn;\u0026thinsp;27.86\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e290.00\u0026thinsp;\u0026plusmn;\u0026thinsp;182.61\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.192\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"4\"\u003e\u003cb\u003eNotes\u003c/b\u003e: CMT: Central macular thickness; ΔCMT: Differences in CMT before and after edema recurrence.\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003c/div\u003e"},{"header":"4. Discussion","content":"\u003cp\u003eThis is a retrospective study. This study compared the efficacy of surgical and injection treatments for patients with persistent or recurrent edema who had previously received intravitreal injection treatment for RVO-ME. The surgery group was treated with subretinal BSS injection after vitrectomy and ILM peeling. This procedure has not been used in the treatment of RVO-ME in previous studies. We aimed to compare the effectiveness of this procedure with medical therapy in improving visual acuity, resolving edema, and recurrence.\u003c/p\u003e\u003cp\u003eIn previous studies,\u003csup\u003e\u003cspan additionalcitationids=\"CR15 CR16\" citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e\u003c/sup\u003e vitrectomy with or without ILM peeling for the treatment of RVO-ME has improved visual acuity compared with that before surgery, with clear long-term effects. These findings are similar to our results. In the clinic, repeated anti-VEGF therapy is necessary to maintain long-term visual stability and prevent visual loss in patients with RVO-ME.\u003csup\u003e\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e\u003c/sup\u003e In our study, the visual improvement of patients with injection therapy was limited and did not achieve the dramatic effect of surgery. In terms of the long-term treatment of RVO-ME, the visual efficacy of anti-VEGF therapy in patients with recurrent edema was reduced.\u003csup\u003e\u003cspan additionalcitationids=\"CR19\" citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e\u003c/sup\u003e This may be related to the damage of the retinal structure caused by repeated edema. Second, related to the ceiling effect, patients with poor baseline visual acuity had a better treatment effect than those with better baseline visual acuity.\u003c/p\u003e\u003cp\u003eIn our study, vitrectomy combined with internal limiting membrane peeling and subretinal injection of BSS was effective for ME. In our follow-up records, edema resolution was mostly observed at 1 week after surgery. Other studies have mentioned that the possible mechanisms of PPV combined with ILM peeling to improve RVO-ME included the release of traction, removal of angiogenic agents, and improvement of retinal oxygenation.\u003csup\u003e\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e,\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e\u003c/sup\u003e In addition, based on the previous application of subretinal BSS injection in DME and severe idiopathic epiretinal membranes,\u003csup\u003e\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e,\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e\u003c/sup\u003e we hypothesized that this treatment could dilute the accumulation of inflammatory factors in the retina, increase retinal oxygenation, and promote circulation, thereby improving persistent edema. In our study, the injection site was chosen based on the 2\u0026ndash;3 optic disk diameters from the macula to reduce unnecessary mechanical damage to the macula and ensure that BSS played a therapeutic role in ME.\u003c/p\u003e\u003cp\u003eIn terms of recurrence, surgical treatment showed advantages in recurrence rate and number. RVO-ME may be a chronic and long-term condition, and patients with this condition present with recurrent edema that requires long-term repeated anti-VEGF injection therapy for maintenance.\u003csup\u003e\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e\u003c/sup\u003e The mean number of ranibizumab injections up to month 12 is 8.1. \u003csup\u003e\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e\u003c/sup\u003e Half equire at least three injections annually thereafter, and some still need up to six injections in the fourth year. \u003csup\u003e\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e\u003c/sup\u003e If the injection frequency is not sufficient according to the treatment plan, the therapeutic effect is difficult to guarantee. Under pro re nata regimens, an insufficient number of follow-up visits can delay detection of recurrent edema, increasing the risk of undertreatment and subsequent neovascularization.\u003csup\u003e\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e\u003c/sup\u003e The macula undergoes repeated relapses of edema, which damage the photoreceptors. Previous studies have found that significant improvement in retinal thickness is not accompanied by a significant increase in BCVA, and there is no simple linear relationship between retinal thickness and visual acuity.\u003csup\u003e\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e,\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e\u003c/sup\u003e This aligns with our findings: while edema in the injection group resolved after retreatment, visual acuity did not improve significantly. In contrast, the surgery group demonstrated a more stable treatment effect. In addition, our study showed that CMT was lower in the surgery group compared with that in the injection group in patients with recurrence. This may be related to the dilution of inflammatory factors by BSS as well as the aforementioned improvement in oxygenation. which helps disrupt the vicious cycle that contributes to chronic ME.\u003csup\u003e\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e\u003c/sup\u003e Surgical intervention thus appears to reduce both the frequency and severity of edema recurrence, providing visual and anatomical benefits, improving quality of life, and reducing the burden of repeated treatment.\u003c/p\u003e\u003cp\u003eThe safety of subretinal injection of BSS has been confirmed in many studies. In clinical applications the injection can be ensured by controlling the injection dose and pressure using methods similar to our self-made injection device. With the updating of equipment, such as iOCT, the operation of subretinal injections can be visualized. It can assist surgeons with observing the macular area morphology during the injection. The retina bulges rapidly during the injection and the surgeon can judge timely whether there is an iatrogenic macular hole due to pressure on the retina. In our study, no macular hole formation was observed. In addition, the depth of the needle can be observed using iOCT to avoid damage to the RPE, which affects retinal function. All the above ensure that the technique of subretinal BSS injections can be safely performed during surgery.\u003c/p\u003e\u003cp\u003eIn summary, vitrectomy combined with internal limiting membrane peeling and subretinal BSS injection was effective and safe for patients with RVO with persistent or recurrent edema in our study. It provides advantages in improving visual acuity and maintaining retinal morphology. This study compared first-line anti-VEGF therapy as a control group and demonstrated that surgery can achieve the same or even better treatment results. A possible limitation is that this study was retrospective and therefore had limited clinical data.\u003c/p\u003e"},{"header":"5. Conclusions","content":"\u003cp\u003eIn our study, vitrectomy combined with internal limiting membrane peeling and subretinal BSS injection was effective and safe for patients with RVO with persistent or recurrent edema.Vitrectomy combined with internal limiting membrane peeling and subretinal BSS injection improves the visual acuity of patients with RVO-ME, reduces edema, and lowers recurrence.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eanti-VEGF \u0026nbsp; anti-vascular endothelial growth factor\u003c/p\u003e\n\u003cp\u003eBCVA \u0026nbsp; \u0026nbsp; \u0026nbsp; Best corrected visual acuity\u003c/p\u003e\n\u003cp\u003eBSS\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;Balanced salt solution\u003c/p\u003e\n\u003cp\u003eCMT \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Central macular thickness\u003c/p\u003e\n\u003cp\u003eDME\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Diabetic macular edema\u003c/p\u003e\n\u003cp\u003eDM \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; Diabetes mellitus;\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eHBP \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;High blood pressure\u003c/p\u003e\n\u003cp\u003eILM \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Internal limiting membrane\u003c/p\u003e\n\u003cp\u003eIOP \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; Intraocular pressure\u003c/p\u003e\n\u003cp\u003eME\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Macular edema\u003c/p\u003e\n\u003cp\u003eRPE \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Retinal pigment epithelium\u003c/p\u003e\n\u003cp\u003eRVO\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;Retinal vein occlusion\u003c/p\u003e\n\u003cp\u003eRVO-ME \u0026nbsp; \u0026nbsp;Macular edema secondary to retinal vein occlusion\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003e\u003cem\u003eEthics approval and consent to participate\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was conducted in accordance with the principles of the Declaration of Helsinki. Informed consent was obtained from all the patients and was approved by the Clinical Trials Ethics Committee of Tianjin Medical University Eye Hospital (2025KY-03).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eAvailability of data and materials\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll data generated or analysed during this study are included in this published article\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eCompeting interests\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare no conflicts of interest or financial relationships that could influence this\u0026nbsp;research.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eFunding\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e1.Tianjin Binhai New Area Health Commission Project (No. 2023BWKZ006).\u003c/p\u003e\n\u003cp\u003e2.Tianjin Key Medical Discipline (Specialty) Construction Project (TJYXZDXK-037A).\u003c/p\u003e\n\u003cp\u003e3.The Science\u0026amp;Technology Development Fund of Tianjin Education Commission for Higher Education (No.2022ZD058).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eAuthors\u0026apos; contributions\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eConception and design of study: Yue Pan, Xiang Zhang, and Bojie Hu.\u003c/p\u003e\n\u003cp\u003eClinical guidance and surgical implementation: Wenbo Li, Xiaorong Li and Bojie Hu.\u003c/p\u003e\n\u003cp\u003eAcquisition and statistical analysis of data: Yue Pan, Jiaxing Chi, Chang Liu and Mengqi An.\u003c/p\u003e\n\u003cp\u003eInterpretation of data: Yue Pan, Xiang Zhang, Qinning Xie and Zetong Nie.\u003c/p\u003e\n\u003cp\u003eDrafting and critical revision: Yue Pan, Xiang Zhang, Wenbo Li and Bojie Hu.\u003c/p\u003e\n\u003cp\u003eSupervision: Wenbo Li and Bojie Hu.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eRogers S, McIntosh RL, Cheung N, et al. The Prevalence of Retinal Vein Occlusion: Pooled Data from Population Studies from the United States, Europe, Asia, and Australia. \u003cem\u003eOphthalmology\u003c/em\u003e. 2010;117(2):313. doi:10.1016/j.ophtha.2009.07.017\u003c/li\u003e\n\u003cli\u003eAscaso FJ, Huerva V, Grzybowski A. The Role of Inflammation in the Pathogenesis of Macular Edema Secondary to Retinal Vascular Diseases. \u003cem\u003eMediators Inflamm\u003c/em\u003e. 2014;2014:432685. doi:10.1155/2014/432685\u003c/li\u003e\n\u003cli\u003eTadayoni R, Waldstein SM, Boscia F, et al. Sustained Benefits of Ranibizumab with or without Laser in Branch Retinal Vein Occlusion: 24-Month Results of the BRIGHTER Study. \u003cem\u003eOphthalmology\u003c/em\u003e. 2017;124(12):1778-1787. doi:10.1016/j.ophtha.2017.06.027\u003c/li\u003e\n\u003cli\u003eYoon YH, Kim JW, Lee JY, et al. Dexamethasone Intravitreal Implant for Early Treatment and Retreatment of Macular Edema Related to Branch Retinal Vein Occlusion: The Multicenter COBALT Study. \u003cem\u003eOphthalmologica\u003c/em\u003e. 2018;240(2):81-89. doi:10.1159/000487547\u003c/li\u003e\n\u003cli\u003eGiuffr\u0026egrave; C, Cicinelli MV, Marchese A, Coppola M, Parodi MB, Bandello F. Simultaneous intravitreal dexamethasone and aflibercept for refractory macular edema secondary to retinal vein occlusion. \u003cem\u003eGraefes Arch Clin Exp Ophthalmol\u003c/em\u003e. 2020;258(4):787-793. doi:10.1007/s00417-019-04577-8\u003c/li\u003e\n\u003cli\u003eNamvar E, Yasemi M, Nowroozzadeh MH, Ahmadieh H. Intravitreal Injection of Anti-Vascular Endothelial Growth Factors Combined with Corticosteroids for the Treatment of Macular Edema Secondary to Retinal Vein Occlusion: A Systematic Review and Meta-Analysis. \u003cem\u003eSemin Ophthalmol\u003c/em\u003e. 2024;39(1):109-119. doi:10.1080/08820538.2023.2249527\u003c/li\u003e\n\u003cli\u003eYamada H, Imai H, Tetsumoto A, et al. Cystotomy with or without fibrinogen clot removal for refractory cystoid macular edema secondary to branch retinal vein occlusion. \u003cem\u003eSci Rep\u003c/em\u003e. 2021;11:8460. doi:10.1038/s41598-021-88149-z\u003c/li\u003e\n\u003cli\u003eYuan Q, Gao Y, Liu Y, Xu H, Wang T, Zhang M. Efficacy of single-dose intravitreal dexamethasone implantation for retinal vein occlusion patients with refractory macular edema: A systematic review and meta-analysis. \u003cem\u003eFront Pharmacol\u003c/em\u003e. 2022;13:951666. doi:10.3389/fphar.2022.951666\u003c/li\u003e\n\u003cli\u003eZhang L, Huang Y, Chen J, Xu X, Xu F, Yao J. Multimodal deep transfer learning to predict retinal vein occlusion macular edema recurrence after anti-VEGF therapy. Heliyon. 2024 Apr 10;10(8):e29334. doi: 10.1016/j.heliyon.2024.e29334.\u003c/li\u003e\n\u003cli\u003eKumagai K, Ogino N, Fukami M, Furukawa M. Removal of foveal hard exudates by subretinal balanced salt solution injection using 38-gauge needle in diabetic patients. \u003cem\u003eGraefes Arch Clin Exp Ophthalmol\u003c/em\u003e. 2020;258(9):1893-1899. doi:10.1007/s00417-020-04756-y\u003c/li\u003e\n\u003cli\u003eHanda S, Dogra M, Tigari B, Katoch D, Singh R. Displacement of submacular hemorrhage with vitrectomy combined with subretinal balanced salt solution and air. \u003cem\u003eRetina\u003c/em\u003e. Published online July 21, 2023. doi:10.1097/IAE.0000000000003879\u003c/li\u003e\n\u003cli\u003eSaab M, Javidi S, Dirani A, et al. Displacement of Retained Subretinal Perfluorocarbon Liquid Through Therapeutic Retinal Detachment Induced by Balanced Salt Solution Injection. Int Med Case Rep J. 2020;13:183-186. https://doi.org/10.2147/IMCRJ.S244166\u003c/li\u003e\n\u003cli\u003eMao Z, You Z. Internal Limiting Peeling in Conjunction with Subretinal Injection of a Balanced Salt Solution in the Macular Region to Treat Refractory Diabetic Macular Edema. Altern Ther Health Med. 2024 Apr 18:AT10722. Epub ahead of print.\u003c/li\u003e\n\u003cli\u003eKumagai K, Ogino N, Fukami M, et al. Long-term outcomes of intravitreous bevacizumab or tissue plasminogen activator or vitrectomy for macular edema due to branch retinal vein occlusion. Clin Ophthalmol. 2019;13:617-626. https://doi.org/10.2147/OPTH.S195600\u003c/li\u003e\n\u003cli\u003eKumagai K, Ogino N, Fukami M, et al. Vitrectomy for macular edema due to retinal vein occlusion. Clin Ophthalmol. 2019;13:969-984. https://doi.org/10.2147/OPTH.S203212\u003c/li\u003e\n\u003cli\u003ePark DH, Kim IT. Long-term effects of vitrectomy and internal limiting membrane peeling for macular edema secondary to central retinal vein occlusion and hemiretinal vein occlusion. \u003cem\u003eRetina Phila Pa\u003c/em\u003e. 2010;30(1):117-124. doi:10.1097/IAE.0b013e3181bced68\u003c/li\u003e\n\u003cli\u003eBaharivand N, Hariri A, Javadzadeh A, Heidari E, Sadegi K. Pars plana vitrectomy and internal limiting membrane peeling for macular edema secondary to retinal vein occlusion. Clin Ophthalmol. 2011;5:1089-93. doi: 10.2147/OPTH.S23164.\u003c/li\u003e\n\u003cli\u003eCampochiaro PA, Sophie R, Pearlman J, et al. Long-term Outcomes in Patients with Retinal Vein Occlusion Treated with Ranibizumab: The RETAIN Study. \u003cem\u003eOphthalmology\u003c/em\u003e. 2014;121(1):209-219. doi:10.1016/j.ophtha.2013.08.038\u003c/li\u003e\n\u003cli\u003eIftikhar M, Mir TA, Hafiz G, et al. Loss of Peak Vision in Retinal Vein Occlusion Patients Treated for Macular Edema. \u003cem\u003eAm J Ophthalmol\u003c/em\u003e. 2019;205:17-26. doi:10.1016/j.ajo.2019.03.029\u003c/li\u003e\n\u003cli\u003eLarsen M, Waldstein SM, Boscia F, et al. Individualized Ranibizumab Regimen Driven by Stabilization Criteria for Central Retinal Vein Occlusion: Twelve-Month Results of the CRYSTAL Study. \u003cem\u003eOphthalmology\u003c/em\u003e. 2016;123(5):1101-1111. doi:10.1016/j.ophtha.2016.01.011\u003c/li\u003e\n\u003cli\u003eNishida A, Kojima H, Kameda T, Mandai M, Kurimoto Y. Five-year outcomes of pars plana vitrectomy for macular edema associated with branch retinal vein occlusion. \u003cem\u003eClin Ophthalmol\u003c/em\u003e. 2017;11:369-375. doi:10.2147/OPTH.S123419\u003c/li\u003e\n\u003cli\u003eLuan R, Liu B, Cai B, Gong Y, Li X. Application of Subretinal Balanced Salt Solution Injection: A Novel technique in treating Severe idiopathic Epiretinal Membrane. \u003cem\u003eRETINA\u003c/em\u003e. Published online May 12, 2022:10.1097/IAE.0000000000004282. doi:10.1097/IAE.0000000000004282\u003c/li\u003e\n\u003cli\u003eIp M, Modi Y, Fekrat S, Gibson K, Boucher N, Arrisi P, Ishii F, Liu Y, Paris LP, Fenech M, Chi GC. Treatment Patterns and Long-Term Outcomes with Anti-VEGF Therapy for Retinal Vein Occlusion: An Analysis of the Vestrum Database. Ophthalmol Retina. 2025 May 27:S2468-6530(25)00251-9. doi: 10.1016/j.oret.2025.05.025.\u003c/li\u003e\n\u003cli\u003eLarsen M, Waldstein SM, Boscia F, et al. Individualized Ranibizumab Regimen Driven by Stabilization Criteria for Central Retinal Vein Occlusion: Twelve-Month Results of the CRYSTAL Study. Ophthalmology. 2016;123(5):1101-1111. https://doi.org/10.1016/j.ophtha.2016.01.011.\u003c/li\u003e\n\u003cli\u003eHamam M, Lagali N, Abdulnour E, Setterud H, Johansson B, Mirabelli P. Real-Life Efficacy of Bevacizumab Treatment for Macular Edema Secondary to Central Retinal Vein Occlusion according to Pro Re Nata or Treat-and-Extend Regimen in Eyes with or without Epiretinal Membrane. \u003cem\u003eJ Ophthalmol\u003c/em\u003e. 2022;2022:6288582. doi:10.1155/2022/6288582\u003c/li\u003e\n\u003cli\u003eScott IU, Oden NL, VanVeldhuisen PC, Ip MS, Blodi BA; SCORE2 Investigator Group. SCORE2 Report 24: Nonlinear Relationship of Retinal Thickness and Visual Acuity in Central Retinal and Hemiretinal Vein Occlusion. Ophthalmology. 2023 Oct;130(10):1066-1072. doi: 10.1016/j.ophtha.2023.05.023. \u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Retinal vein occlusion, Macular edema, Subretinal injection, Balanced salt solution, Anti-vascular endothelial growth factor, Pars plana vitrectomy","lastPublishedDoi":"10.21203/rs.3.rs-7385007/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7385007/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cem\u003e\u003cstrong\u003ePurposes\u003c/strong\u003e\u003c/em\u003e: To investigate the efficacy and safety of subretinal balanced salt solution (BSS) injections for macular edema secondary to retinal vein occlusion (RVO-ME).\u003c/p\u003e\n\u003cp\u003e\u003cem\u003e\u003cstrong\u003eMethods\u003c/strong\u003e\u003c/em\u003e: We retrospectively analyzed 19 eyes of 19 patients characterized by Retinal vein occlusion (RVO) diagnosed usng retinal angiography and persistent or recurrent edema on OCT after at least three standard-dose Anti-vascular endothelial growth factor (anti-VEGF) treatments. The operation group received vitrectomy combined with internal limiting membrane (ILM) peeling and subretinal injection of BSS. The operation group continued to receive intravitreal injection of anti-VEGF drugs. The results of visual acuity, retinal morphology, and recurrence were analyzed and compared between the two groups after treatment.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003e\u003cstrong\u003eResults\u003c/strong\u003e\u003c/em\u003e\u003cstrong\u003e: \u003c/strong\u003eThe best corrected visual acuity (BCVA) of the surgery group improved (0.60 ± 0.45, P = 0.006) and the best visual acuity reached the same level as that of the injection group (0.53 ± 0.49, P = 0.622). The minimum Central macular thickness (CMT) of the two groups after intervention was 266.40 ± 52.08 µm and 221.89 ± 38.62 µm (P = 0.051), respectively, and both groups exhibited reduced CMT and edema (P \u0026lt; 0.001, P = 0.008). The recurrence rate of the surgery group was 40%, which was lower than that of the injection group (88.9%, P = 0.051). The CMT were 473.00 ± 45.44 µm and 586.89 ± 169.18 μm (P = 0.225) at recurrence.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003e\u003cstrong\u003eConclusions\u003c/strong\u003e\u003c/em\u003e: Vitrectomy with ILM peeling and subretinal BSS injection may enhance visual acuity, reduce macular edema, and lower the recurrence rate in patients with RVO-ME.\u003c/p\u003e","manuscriptTitle":"Subretinal Injection of Balanced Salt Solution for Macular Edema Secondary to Retinal Vein Occlusion","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-09-01 09:28:58","doi":"10.21203/rs.3.rs-7385007/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"0ae6c622-affd-4901-bb67-c1dc9d99eafb","owner":[],"postedDate":"September 1st, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-09-07T09:53:39+00:00","versionOfRecord":[],"versionCreatedAt":"2025-09-01 09:28:58","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-7385007","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7385007","identity":"rs-7385007","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}