Clinical efficacy of conbercept combined with micropulse laser in patients with polypoidal choroidal vasculopathy

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Methods In this prospective, randomized controlled trial conducted from February 2023 to April 2024, 52 patients (52eyes) with PCV at ### hospital were enrolled. Participants were randomized into a conbercept monotherapy group (27cases, 27eyes) and a combination treatment group (conbercept plus micropulse laser(MPL); 25cases, 25eyes). After an initial series of three intravitreal injections, all patients followed the Treat & Extend (T&E) protocol. Aqueous humor samples were collected before each of the first three injections, and cytokines levels were measured after the sample collection. The combined treatment group received a 577nm MPL application two weeks following the first injection. The best corrected visual acuity (BCVA) 、central macular thickness (CMT) and total macular volume (TMV) of each group were assessed monthly for three months. Results From the first to the third month post-injection, both treatment groups showed improvements in BCVA and reductions in CMT and TMV, with the combined treatment group demonstrating significantly greater improvements at each monthly evaluation (P < 0.05). Additionally, levels of aqueous humor cytokines, including VEGF-A, IL-5, MCP-1, and Ang-2, were significantly reduced in both groups. Reductions in VEGF-A and MCP-1 concentrations were positively correlated with improvements in BCVA, CMT, and TMV (P < 0.01). Conclusion Conbercept combined with MPL therapy demonstrates superior clinical efficacy compared to intravitreal injection of Conbercept alone in patients with PCV. Furthermore, changes in VEGF-A and MCP-1 levels may serve as predictive markers for improvements in visual acuity and retinal morphology in these patients. conbercept micropulse laser polypoidal choroidal vasculopathy cytokinine best corrected visual acuity central macular thickness total macular volume monocyte chemotactic protein-1 Figures Figure 1 Figure 2 Figure 3 Introduction Polypoidal choroidal vasculopathy (PCV) is a choroidal vascular disease mainly affecting the macular region and is considered a unique subtype of age-related macular degeneration (AMD) 1 . It is characterized by abnormal choroidal vascular network, including choroidal vasodilation and polypoid lesions prone to leakage and hemorrhage. PCV has a notably high incidence among East Asian populations 2 – 5 , Intravitreal injection of anti-vascular endothelial growth factor (VEGF) agents is the currently first-line treatment for PCV 6 . However, some patients exhibit limited responsiveness to anti-VEGF therapy, highlighting the need for alternative or adjunctive treatments. Micropulse Laser (MPL) is an advanced optical therapy technology designed to minimize thermal damage to retina tissue by dividing the laser energy in microsecond pulses. This approach allows for precise energy transmission, reducing the risk of retinal burns and other side effects associated with traditional laser therapy. MPL is commonly used to treat various retinal diseases 7 – 9 , such as diabetic macular edema, chronic central serous choroidopathy, retinal vein occlusion with macular edema. Currently, there is limited research on combining anti-VEGF therapy with MPL in PCV treatment. In this study, 52 patients (52 eyes) with PCV were randomly divided into two groups: a conbercept monotherapy group and a combination therapy group receiving both conbercept and MPL. This study aims to observe the prognostic outcomes and aqueous humor cytokine changes in these patients, offering a potential new approach to PCV management. Materials and Methods Subjects This study enrolled 52 treatment-naive PCV patients (52 eyes) from February 2023 to April 2024. Among them, 27 of them were randomly selected for intravitreal injection of conbercept, and the remaining 25 patients underwent 577nm MPL two weeks after the first injection. Prior to each of the first three injections, aqueous humor samples were collected and transferred to a -80°C freezer. Cytokines in aqueous humor were detected by Luminex platform, and the best corrected visual acuity (BCVA), central macular thickness (CMT) and total macular volume(TMV) were measured before treatment and then monitored monthly from the first to the third month after injection. Inclusion criteria: (1) Age above 50, (2) Clinically diagnosed by indocyanine green angiography (ICGA) or optical coherence optical tomography (OCT); Exclusion criteria: (1) serious systemic diseases, such as uncontrollable hypertension, diabetes or various infectious diseases; (2) Previous or ongoing cancer treatment, taking hormones or immunosuppressive drugs; (3) Other inflammatory or vascular diseases appeared in the eyes during the treatment. This study follows the principles of Helsinki Declaration on research involving human subjects, and has been discussed and approved by the Medical Ethics Committee of our hospital ((R)2022-012). All patients provided informed consent after being fully briefed on the risks associated with the treatment plan. Data Acquisition and Processing All enrolled patients underwent detailed medical history inquiry and comprehensive preoperative eye examination, including BCVA test, intraocular pressure examination (Nidek, Japan), slit lamp examination. Additional imaging included OCT (Optovue, USA) to document CMT and TMV and ICGA (Heidelberg, Germany) for diagnosis confirmation. All patients were instructed to administer levofloxacin eye drops (0.5%, 5 ml, Santen, Japan) four times daily starting three days before injection. The eye dressings were removed two hours post-injection, and the intraocular pressure was measured. Patients continued levofloxacin drops four times daily for one week post-injection. The intravitreal drug administered was Conbercept Eye Injection (Chengdu Kanghong Biotechnology Co, Ltd., China), with a dose of 0.05 ml per injection. Intravitreal Injection Intravitreal injections were performed in the sterile operating room, and topical anesthesia was performed with Elcaine eye drops. After disinfection of conjunctival sac with 5% povidone iodine, the injection was administered 3.5 - 4.0mm posterior to the corneal limbus. Approximately 100 microliters of aqueous humor samples were collected from both groups under aseptic conditions. Samples were temporarily stored in liquid nitrogen, and then transferred to a -80°C refrigerator for storage. All injections were performed by the same deputy chief physician at our hospital. MPL The combined treatment group was treated with MPL 2 weeks after the first injection. The laser with the threshold of 577nm from EASYRET was selected. Using a Volk Area Centralis lens (0.94X), the spot size was set to 160 µm, with an exposure time of 0.2 seconds and a duty cycle of 5%. The power was initially set to 600 mW and gradually increased near the vascular arch for titration test until a newly visible spot appeared, determining the threshold power. 50% of the threshold power adjustment is used as the power parameter of micropulse mode during treatment, and grid-like photocoagulation in macular area is performed and the results are recorded. This laser treatment was conducted by a different deputy chief physician at our hospital. Cytokine Measurement Assays Four cytokines in aqueous humor, vascular endothelial growth factor -A(VEGF-A), interleukin-5 (IL-5), monocyte chemoattractant protein -1 (MCP-1) and angiotensin-2 (Ang-2), were quantified using the Luminex platform with the HAGPIMAC kit (Merck, USA). Data were analyzed using the xPONENT Flex Map 3D system, employing a five-parameter curve fitting algorithm with Milliplex Analyst 6.1 software. Statistical Analysis Data analysis was conducted using SPSS 26.0., and continuous variables were compared using independent sample T-tests, while categorical data, such as gender and eye type, were analyzed with rank sum tests. BCVA was measured with standard logarithmic visual acuity chart, which was converted into the logarithm of the minimum resolution angle (LogMar). CMT was defined as the distance from the retinal internal limiting membrane to the pigment epithelium at the fovea. The cross-sectional image of macular area is scanned and drawn by OCT, and TMV was calculated using RTVue software based on cross-sectional OCT images of the macular area. Normally distributed variables are summarized by mean and standard deviation, while non-normally distributed variables are presented as median and interquartile range. A repeated measures ANOVA was used to compare BCVA, CMT, TMV, and cytokine concentrations between the two groups before and after treatment, as well as prior to each of the three injections. Statistical significance was set at an α level of 0.05, with P < 0.05 indicating significance. Results Patient characteristics A total of 52 patients (52 eyes) participated in this study. The monotherapy group included 27 patients (10 males and 17 females; 15 right eyes and 12 left eyes), with a mean age of 67.74 ± 9.24 years. The combination treatment group consisted of 25 patients (12 males and 13 females; 14 right eyes and 11 left eyes) with an average age of 71.64 ± 8.89 years. There were no statistically significant differences between the groups in terms of age (P = 0.128), gender (P = 0.429), or laterality (P = 0.975), as detailed in Table 1 . Table 1 Patient characteristics of the study population Conbercept group Combination treatment group Z/t P Gender male 10 12 −0.792 0.429 female 17 13 Eyes OD 15 14 −0.032 0.975 OS 12 11 Age (ys) 67.74 ± 9.24 71.64 ± 8.89 −1.548 0.128 Therapeutic efficacy Both treatment groups demonstrated improved visual acuity post-treatment, with the combined treatment group exhibiting better outcomes compared to the conbercept monotherapy group at the first month (t = 2.811,p = 0.028), the second month (t = 3.085,p = 0.013) and the third month (t = 2.879,p = 0.024),as shown in Table 2 and Fig. 1 . CMT decreased significantly in both groups after treatment. and the CMT in the combined treatment group was lower than that in conbercept group in the first month (t = 2.837,p = 0.026), the second month (t = 2.925,p = 0.021) and the third month (t = 2.966, p = 0.018),as shown in Table 3 and Fig. 2 . TMV also improved in both groups; however, the TMV in the combination treatment group was significantly lower than that in the conbercept group at the second month (F = 2.729, P < 0.05) and the third month (F = 2.973, P 0.05),as shown in Table 4 and Fig. 3 . Table 2 Comparison of BCVA (Logmar) at different time points in the two groups Conbercept group (n = 27) (mean ± SD) Combined treatment group (n = 25) (mean ± SD) t P value Base line 0.791 ± 0.175 0.752 ± 0.272 0.937 0.825 First month 0.498 ± 0.134 0.399 ± 0.107 2.811 0.028 Second month 0.454 ± 0.127 0.353 ± 0.103 3.085 0.013 Third month 0.392 ± 0.130 0.301 ± 0.089 2.879 0.024 (Note: *refers to the comparison between the two groups, the difference is statistically significant (P < 0.05)) Table 3 Comparison of CMT (µm) at different time points in the two groups Conbercept group (n = 27) (mean ± SD) Combined treatment group (n = 25) (mean ± SD) t P value Base line 394.196 ± 70.017 408.160 ± 71.828 0.704 0.930 First month 353.556 ± 62.702 308.400 ± 51.890 2.837 0.026 Second month 322.148 ± 61.815 179.920 ± 40.887 2.925 0.021 Third month 287.778 ± 49.427 250.120 ± 42.033 2.966 0.018 Table 4 TMV at different time points in the two groups (mm 3 ) The situation of the comparison Conbercept group (n = 27) (mean ± SD) Combined treatment group(n = 25) (mean ± SD) F P value Base line 10.090 ± 1.887 10.290 ± 1.840 0.385 0.9921 First month 9.846± 1.680 8.870 ± 1.114 2.485 0.0651 Second month 9.367 ± 1.411 8.455 ± 0.973 2.729 0.035 Third month 8.800 ± 1.022 7.994 ± 0.959 2.937 0.020 Correlation between cytokines in aqueous humor and clinical outcomes The concentrations of cytokines were measured in the first and second months, and differences in BCVA, CMT, and TMV from baseline were analyzed to explore the correlations between cytokine levels in aqueous humor and these clinical outcomes. In the first month, The difference of VEGF-A was positively correlated with BCVA, CMT and TMV (r = 0.875, 0.457, 0.475, respectively). The difference of IL-5 was positively correlated with the change of CMT and TMV (r = 0.380, 0.454, respectively), but did not correlate significantly with BCVA (P > 0.05). MCP-1 exhibited a positive correlation with BCVA, TMV and CMT (r = 0.449, 0.728, 0.742, respectively). Conversely, the difference in Ang-2 concentration was negatively correlated with the change in BCVA (r = -0.288), but did not show significant correlation with changes in CMT and TMV (P > 0.05),as detailed in Table 5 . In the second month, the change in VEGF-A remained positively correlated with changes in BCVA, CMT, and TMV (r = 0.854, 0.541, and 0.718, respectively). The change in IL-5 was also positively correlated with BCVA, CMT, and TMV (r = 0.413), while MCP-1 showed positive correlations with BCVA and CMT (r = 0.670 and 0.694, respectively). However, the change in Ang-2 was not significantly correlated with BCVA, CMT, or TMV (P > 0.05),as detailed in Table 6 . Table 5 Correlation analysis between cytokine concentration difference and BCVA, CMT and TMV at the first month Cytokine mass concentration difference BCVA change value CMT change value TMV change value r P value r P value r P value VEGF-A 0.875 <0.001 a 0.457 0.001 a 0.475 <0.001 a IL−5 0.218 0.121 a 0.380 0.005 a 0.454 0.001 a MCP−1 0.449 0.001 a 0.728 <0.001 a 0.742 <0.001 a Ang−2 −0.288 0.038 a −0.034 0.813 a −0.026 0.085 a (a:Spearman rank correlation analysis) Table 6 Correlation analysis between cytokine concentration difference and BCVA, CMT and TMV at the second month Cytokine mass concentration difference BCVA change value CMT change values TMV change values r P value r P value r P value VEGF-A 0.854 <0.001 a 0.541 <0.001 a 0.718 <0.001 a IL−5 0.413 <0.001 a 0.293 0.035 a 0.485 <0.001 a MCP−1 0.670 <0.001 a 0.694 <0.001 a 0.470 <0.001 a Ang−2 −0.110 0.437 a −0.014 0.923 a −0.085 0.550 a (a:Spearman rank correlation analysis) Discussion Conbercept is a fusion protein anti-VEGF drug that targets all VEGF-A isoforms, placental growth factor and VEGF-B, and has the effects of reducing vascular permeability and tissue vasodilation 10 . The landmark AURORA study 11 showed that 0.5 and 2.0 mg Conbercept could effectively reduce macular edema and improved the visual and anatomical outcomes for PCV patients. However, while beneficial, conbercept does not address the underlying etiology of PCV, leading to high recurrence rates and necessitating repeated injections. Persistent dysfunction of retinal pigment epithelial cells and photoreceptor damage remain significant contributors to central vision loss in these patients. In the 1990s, Pankratov introduced the MPL mode, and used the sub-domain reaction energy to treat fundus lesions, which can selectively act on retinal pigment epithelial cells, and normal retinal pigment epithelial cells will regenerate to repair the damaged areas and restore the retinal barrier, suggested that it could be an effective choice for PCV treatment 12 . MPL is a kind of short and high-frequency repetitive pulse laser, which includes a series of tiny and repeatable "on-off" pulses in a complete laser exposure process. The single pulse time t includes the action time ON and the intermittent time OFF. The ratio of the ON time and the total exposure time (ON/OFF) is called duty cycle (DC), which represents the effective laser transmission time and can be adjusted independently to realize the fine control of photothermal effect and effective space limitation 13 . During the laser action time, RPE cells absorb the laser and convert the laser light energy into heat energy. During the intermittent time, RPE cells diffuse the absorbed heat energy locally. The spread of heat energy is related to the pulse time. The shorter the laser time, the closer the heat propagation distance, and the less damage to the surrounding tissues. The main action range of MPL is limited to RPE cells, with little damage to the adjacent tissues, and there is no visible laser spot on the retina in the treatment area 14,15 . The subthreshold energy provided by MPL stimulates the production of heat shock proteins (HSPs), which are ubiquitous and highly conserved molecules, and protect cells from any kind of stress by blocking apoptosis and inflammatory pathways that lead to cell damage 16 . In addition, compared with traditional photocoagulation, MPL can also protect color vision and maintain retinal contrast sensitivity 17 . Iovino 18 and other studies have confirmed that MPL therapy can absorb subretinal fluid in central serous chorioretinopathy and retinal fluid in various diseases. As a new non-invasive and effective treatment method, MPL therapy is a cheap and safe treatment method with no adverse reactions to patients. It has a high curative effect in the treatment of subretinal fluid and can be used as the first-line treatment in clinic 19 . Our study demonstrated that after three months of treatment, both groups—conbercept monotherapy and conbercept combined with MPL showed significant improvement in BCVA, with the combined treatment group achieving superior visual acuity outcomes compared to the monotherapy group. Conbercept could rapidly alleviated disease severity, while subsequent MPL treatment provided biological modulation, enhancing therapeutic effects. CMT and TMV, essential markers reflecting subretinal fluid absorption, were used to quantitatively assess retinal morphology changes through OCT before and after conbercept injection. Both treatment approaches reduced CMT and TMV, with the combined treatment showing a more pronounced clinical benefit. This effect may stem from effect of conbercept on reducing macular edema, while MPL, with its selective and controlled pulse sequences, targets the pathological tissue over a sustained period. The synergy between conbercept and MPL thus enhances the therapeutic impact, indicating that conbercept combined with MPL is an effective approach for treating PCV. The results showed that VEGF-A, IL-5, MCP-1 and Ang-2 decreased gradually following treatment, and the changes of VEGF-A and MCP-1 were positively correlated with the changes of BCVA, CMT and TMV in the first month and the second month. Many studies have confirmed that VEGF-A was the key pathogenic factor of wet age-related macular degeneration (nAMD) and PCV, with the reduction of VEGF-A concentrations being a primary treatment target in these conditions 20-22 . Researchers also highlights that inflammatory cytokines such as IL-23, MCP-1, VEGF and TNF-α are related to the pathogenesis of PCV 23-26 . Zhang 27 and colleagues found triamcinolone acetonide more effective than anti-VEGF agents in treating PCV with hemorrhagic retinal detachment, reinforcing the association between PCV and inflammatory cytokines. Our results also fully showed that PCV was not only a neovascular proliferative disease, but also may involved inflammatory factors or other factors. Consequently, the combined anti-VEGF and MPL approach provided a better therapeutic effect for PCV patients compared to anti-VEGF monotherapy, emphasizing the multifactorial nature of PCV and the potential advantages of a multi-modal treatment strategy. MCP-1 (monocyte chemoattractant protein -1), also known as chemokine (CC motif) ligand 2(CCL2), is a member of the CC chemokine family and plays a crucial role in the inflammatory response by attracting inflammatory cells, leading to the progression of various diseases through mechanisms involving the migration and infiltration of monocytes, macrophages, and other cells 28-30 . Agawa 31 , Hu 32 and Sakamoto 33 found that the levels of MCP-1 and IP-10 in aqueous humor of PCV patients were higher, while Kato3 4 found that MCP-1 and C3a were significantly higher in PCV and nAMD than in the control group. MCP-1 has chemotactic activity on monocytes and basophils, participates in angiogenesis by stimulating macrophages and RPE, and mediates the increase of VEGF production, which may plays a key role in the development of CNV in PCV 35 . Sun and colleagues 36 indicated that various cytokines, including MCP-1, are related to central macular thickness (CMT) before and after treatment with rezumab in PCV patients, suggesting that both angiogenic and inflammatory factors drive angiogenesis in PCV. The results of our study showed that the change of MCP-1 concentration was positively correlated with BCVA, CMT and TMV, suggesting that MCP-1 may serve as a predictor of visual improvement and retinal morphological changes in PCV patients following anti-VEGF treatment, which could be significant for evaluating prognosis in PCV management. To sum up, with the development of population aging, the prevalence of PCV is on the rise, presenting ongoing challenges in clinical diagnosis and management. To explore the etiology and pathogenesis of PCV, Improving the understanding of diagnosis and treatment of PCV will help to improve the diagnosis rate of PCV, help to comprehensively judge the prognosis of patients with PCV and adopt personalized treatment, and provide guidance for saving the vision of patients with PCV. Anti-VEGF combined with MPL therapy is more effective than simple anti-VEGF drugs in enhancing vision, reducing CRT, decreasing TMV area, with a high safety profile. Our findings highlight a promising direction for clinical PCV management with notable potential for broader application. However, the study's limited sample size and short three-month follow-up period warrant further research to evaluate the long-term efficacy of this combined approach. Declarations Ethical Approval The studies involving human participants were reviewed and approved by Ethical Committee of Anhui NO.2 Provincial People’s hospital ((R)2022-012). The patients/participants provided their written informed consent to participate in this study and agreed to publish the results. Funding This work was supported by Foreign Expert Project of Anhui Provincial Science and Technology Department (S202234017) and Tianjin Health Research Project (TJWJ2024QN026) Author Contribution Shao collected aqueous humor samples.Xue was in charge of micropulse laser therapy.Yin and Ma are collected clinical patient information.Liu and Lu wrote the main manuscript textSun was in charge of the statistical processing of data. References Cheung CMG, Lai TYY, Teo K, Ruamviboonsuk P, Chen SJ, Kim JE, Gomi F, Koh AH, Kokame G, Jordan-Yu JM, Corvi F, Invernizzi A, Ogura Y, Tan C, Mitchell P, Gupta V, Chhablani J, Chakravarthy U, Sadda SR, Wong TY, Staurenghi G, Lee WK (2021) Polypoidal Choroidal Vasculopathy: Consensus Nomenclature and Non-Indocyanine Green Angiograph Diagnostic Criteria from the Asia-Pacific Ocular Imaging Society PCV Workgroup. 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Invest Ophthalmol Vis Sci 53:3424–3430 Kikuchi M, Nakamura M, Ishikawa K, Suzuki T, Nishihara H, Yamakoshi T, Nishio K, Taki K, Niwa T, Hamajima N, Terasaki H (2007) Elevated C-reactive protein levels in patients with polypoidal choroidal vasculopathy and patients with neovascular age-related macular degeneration. Ophthalmology 114:1722–1727 Zhang K, Chen Y, Sun X, Zhong Q, Lin L, Gao Y, Hong F (2018) Periocular triamcinolone acetonide injection for treating polypoidal choroidal vasculopathy concurrent with hemorrhagic retinal detachment. Med (Baltim) 97:e12464 Zhu X, Meng J, Han C, Wu Q, Du Y, Qi J, Wei L, Li H, He W, Zhang K, Lu Y (2023) CCL2-mediated inflammatory pathogenesis underlies high myopia-related anxiety. Cell Discov 9(1):94. 10.1038/s41421-023-00588-2 Deliyanti D, Suphapimol V, Ang P, Tang X, Jayasimhan A, Wilkinson-Berka JL (2023) Early Depletion of Neutrophils Reduces Retinal Inflammation and Neovascularization in Mice with Oxygen-Induced Retinopathy. Int J Mol Sci 24(21):15680. 10.3390/ijms242115680 Ferreira LB, Williams KA, Best G, Haydinger CD, Smith JR (2023) Inflammatory cytokines as mediators of retinal endothelial barrier dysfunction in non-infectious uveitis. Clin Transl Immunol 12(12):e1479. 10.1002/cti2.1479 Agawa T, Usui Y, Wakabayashi Y, Okunuki Y, Juan M, Umazume K, Kezuka T, Takeuchi M, Yamauchi Y, Goto H (2014) Profile of intraocular immune mediators in patients with age-related macular degeneration and the effect of intravitreal bevacizumab injection. Retina 34(9):1811–1818. 10.1097/IAE.0000000000000157 Hu J, Leng X, Hu Y, Atik A, Song X, Li Z, Liu Y, Lu L (2016) The Features of Inflammation Factors Concentrations in Aqueous Humor of Polypoidal Choroidal Vasculopathy. PLoS ONE 11(1):e0147346. 10.1371/journal.pone.0147346 Sakamoto S, Takahashi H, Tan X, Inoue Y, Nomura Y, Arai Y, Fujino Y, Kawashima H, Yanagi Y (2018) Changes in multiple cytokine concentrations in the aqueous humour of neovascular age-related macular degeneration after 2 months of ranibizumab therapy. Br J Ophthalmol 102(4):448–454. 10.1136/bjophthalmol-2017-310284 Epub 2017 Aug 1 Kato Y, Oguchi Y, Omori T, Shintake H, Tomita R, Kasai A, Ogasawara M, Sugano Y, Itagaki K, Ojima A, Machida T, Sekine H, Sekiryu T (2020) Complement Activation Products and Cytokines in Pachychoroid Neovasculopathy and Neovascular Age-Related Macular Degeneration. Invest Ophthalmol Vis Sci 61(13):39. 10.1167/iovs.61.13.39 Long Q, Cao X, Bian A, Li Y (2016) C3a Increases VEGF and Decreases PEDF mRNA Levels in Human Retinal Pigment Epithelial Cells. Biomed Res Int 2016:6958752. 10.1155/2016/6958752 Epub 2016 Sep 22 Sun T, Bai J, Wang M, Liu L, Peng Q (2022) Cytokine profiling in patients with polypoidal choroidal vasculopathy before and after intravitreal injection of ranibizumab. Am J Transl Res 14(10):7147–7155 Additional Declarations No competing interests reported. Cite Share Download PDF Status: Published Journal Publication published 22 Sep, 2025 Read the published version in Lasers in Medical Science → Version 1 posted Editorial decision: Revision requested 04 Jun, 2025 Reviews received at journal 04 Jun, 2025 Reviewers agreed at journal 08 May, 2025 Reviews received at journal 08 Nov, 2024 Reviewers agreed at journal 08 Nov, 2024 Reviewers invited by journal 05 Nov, 2024 Editor assigned by journal 05 Nov, 2024 Submission checks completed at journal 23 Oct, 2024 First submitted to journal 18 Oct, 2024 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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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-5290451","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":369754035,"identity":"1d1bf1da-8d74-409b-a324-474baa8c7207","order_by":0,"name":"Qingyan Liu","email":"","orcid":"","institution":"Anhui NO.2 Provincial People’s hospital","correspondingAuthor":false,"prefix":"","firstName":"Qingyan","middleName":"","lastName":"Liu","suffix":""},{"id":369754036,"identity":"543b1ba1-137e-44dd-bc7f-a29e84d1579b","order_by":1,"name":"Yao Lu","email":"","orcid":"","institution":"Bengbu Medical University","correspondingAuthor":false,"prefix":"","firstName":"Yao","middleName":"","lastName":"Lu","suffix":""},{"id":369754037,"identity":"c722cbf0-2224-4956-a2b7-f2195d80b109","order_by":2,"name":"Shuo Sun","email":"","orcid":"","institution":"Tianjin Medical University Eye Hospital","correspondingAuthor":false,"prefix":"","firstName":"Shuo","middleName":"","lastName":"Sun","suffix":""},{"id":369754038,"identity":"d580dd34-569d-4024-a7b6-94acb12584d5","order_by":3,"name":"Xiao Shao","email":"","orcid":"","institution":"Anhui NO.2 Provincial People’s hospital","correspondingAuthor":false,"prefix":"","firstName":"Xiao","middleName":"","lastName":"Shao","suffix":""},{"id":369754039,"identity":"e6061182-c357-4097-ae64-a7cd85d9bcfd","order_by":4,"name":"Xin Yin","email":"","orcid":"","institution":"Anhui NO.2 Provincial People’s hospital","correspondingAuthor":false,"prefix":"","firstName":"Xin","middleName":"","lastName":"Yin","suffix":""},{"id":369754040,"identity":"a35d417f-41a6-4762-9cbf-b9167e958811","order_by":5,"name":"Shuying Ma","email":"","orcid":"","institution":"Bengbu Medical University","correspondingAuthor":false,"prefix":"","firstName":"Shuying","middleName":"","lastName":"Ma","suffix":""},{"id":369754041,"identity":"49c73490-22a1-4f19-8bdb-e148baa1a52c","order_by":6,"name":"Min Xue","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAx0lEQVRIiWNgGAWjYBAC9nYIzcPA3tj48AMxWngOw7TwHG42liBFCwODRHqbAA9RWph5zKR5KrbJmEs+bGOQYLCT020grMXYmOfMbR7L2YltDwoYko3NDhDQYs/MY/iYt+02j8HtxHYDCYYDidsIaQHaYnCY9x9Qy82DbRI8RGoB2tIA1HKDkWgtbMWGc44BtZxJBAayARF+4WFv3ibxpua2vcHx4w8ffqiwkyOohYGBwwCJY4BTGTJgf0CUslEwCkbBKBjBAABK2jxMmEttyQAAAABJRU5ErkJggg==","orcid":"","institution":"Anhui NO.2 Provincial People’s hospital","correspondingAuthor":true,"prefix":"","firstName":"Min","middleName":"","lastName":"Xue","suffix":""}],"badges":[],"createdAt":"2024-10-18 15:23:25","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-5290451/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-5290451/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1007/s10103-025-04619-0","type":"published","date":"2025-09-22T15:57:54+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":67618751,"identity":"6b36f0de-0f8b-4213-a336-119886fe098c","added_by":"auto","created_at":"2024-10-28 06:52:55","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":52486,"visible":true,"origin":"","legend":"\u003cp\u003eBCVA (Logmar) of patients in two groups at different time points\u003c/p\u003e\n\u003cp\u003e(Note: *refers to the comparison between the two groups, the difference is statistically significant (P \u0026lt;0.05))\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-5290451/v1/2c40f239fd712ca816fff0ac.png"},{"id":67618752,"identity":"f123715b-ff4c-40d7-a7ac-6576cc0379af","added_by":"auto","created_at":"2024-10-28 06:52:56","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":49074,"visible":true,"origin":"","legend":"\u003cp\u003eCMT(μm) of two groups of patients at different time points\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-5290451/v1/35399fba0386516ec99e6bb6.png"},{"id":67618750,"identity":"7952cab2-7549-4014-af47-01172951d53e","added_by":"auto","created_at":"2024-10-28 06:52:55","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":50433,"visible":true,"origin":"","legend":"\u003cp\u003eTMV (mm\u003csup\u003e3\u003c/sup\u003e) of patients in two groups at different time points.\u003c/p\u003e","description":"","filename":"3.png","url":"https://assets-eu.researchsquare.com/files/rs-5290451/v1/57cd4db7616fea187edf6c51.png"},{"id":92430630,"identity":"93cf1d63-e550-4827-9cf0-2d869e4a918d","added_by":"auto","created_at":"2025-09-29 16:07:02","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":946607,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-5290451/v1/0a2f1752-88d3-4642-914d-977104e3ea4b.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Clinical efficacy of conbercept combined with micropulse laser in patients with polypoidal choroidal vasculopathy","fulltext":[{"header":"Introduction","content":"\u003cp\u003ePolypoidal choroidal vasculopathy (PCV) is a choroidal vascular disease mainly affecting the macular region and is considered a unique subtype of age-related macular degeneration (AMD)\u003csup\u003e\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u003c/sup\u003e. It is characterized by abnormal choroidal vascular network, including choroidal vasodilation and polypoid lesions prone to leakage and hemorrhage. PCV has a notably high incidence among East Asian populations\u003csup\u003e\u003cspan additionalcitationids=\"CR3 CR4\" citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u003c/sup\u003e, Intravitreal injection of anti-vascular endothelial growth factor (VEGF) agents is the currently first-line treatment for PCV\u003csup\u003e\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u003c/sup\u003e. However, some patients exhibit limited responsiveness to anti-VEGF therapy, highlighting the need for alternative or adjunctive treatments. Micropulse Laser (MPL) is an advanced optical therapy technology designed to minimize thermal damage to retina tissue by dividing the laser energy in microsecond pulses. This approach allows for precise energy transmission, reducing the risk of retinal burns and other side effects associated with traditional laser therapy. MPL is commonly used to treat various retinal diseases\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, such as diabetic macular edema, chronic central serous choroidopathy, retinal vein occlusion with macular edema.\u003c/p\u003e \u003cp\u003eCurrently, there is limited research on combining anti-VEGF therapy with MPL in PCV treatment. In this study, 52 patients (52 eyes) with PCV were randomly divided into two groups: a conbercept monotherapy group and a combination therapy group receiving both conbercept and MPL. This study aims to observe the prognostic outcomes and aqueous humor cytokine changes in these patients, offering a potential new approach to PCV management.\u003c/p\u003e"},{"header":"Materials and Methods","content":"\u003cp\u003eSubjects\u003c/p\u003e\n\u003cp\u003eThis study enrolled 52 treatment-naive PCV patients (52 eyes) from February 2023 to April 2024. Among them, 27 of them were randomly selected for intravitreal injection of\u0026nbsp;conbercept, and the remaining 25 patients underwent 577nm MPL two weeks after the first injection. Prior to each of the first three injections, aqueous humor samples were collected and transferred to a -80\u0026deg;C freezer. Cytokines in aqueous humor were detected by Luminex platform, and the best corrected visual acuity (BCVA), central macular thickness (CMT) and total macular volume(TMV) were measured before treatment and then monitored monthly from the first to the third month after injection.\u003c/p\u003e\n\u003cp\u003eInclusion criteria: (1) Age above 50, (2) Clinically diagnosed by indocyanine green angiography (ICGA) or optical coherence optical tomography (OCT); Exclusion criteria: (1) serious systemic diseases, such as uncontrollable hypertension, diabetes or various infectious diseases; (2) Previous or ongoing cancer treatment, taking hormones or immunosuppressive drugs; (3) Other inflammatory or vascular diseases appeared in the eyes during the treatment. This study follows the principles of Helsinki Declaration on research involving human subjects, and has been discussed and approved by the Medical Ethics Committee of our hospital ((R)2022-012). All patients provided informed consent after being fully briefed on the risks associated with the treatment plan.\u003c/p\u003e\n\u003cp\u003eData Acquisition and Processing\u003c/p\u003e\n\u003cp\u003eAll enrolled patients underwent detailed medical history inquiry and comprehensive preoperative eye examination, including BCVA test, intraocular pressure examination (Nidek, Japan), slit lamp examination. Additional imaging included OCT (Optovue, USA) to document CMT and TMV and ICGA (Heidelberg, Germany) for diagnosis confirmation. All patients were instructed to administer levofloxacin eye drops (0.5%, 5 ml, Santen, Japan) four times daily starting three days before injection. The eye dressings were removed two hours post-injection, and the intraocular pressure was measured. Patients continued levofloxacin drops four times daily for one week post-injection. The intravitreal drug administered was Conbercept Eye Injection (Chengdu Kanghong Biotechnology Co, Ltd., China), with a dose of 0.05 ml per injection.\u003c/p\u003e\n\u003cp\u003eIntravitreal Injection\u003c/p\u003e\n\u003cp\u003eIntravitreal injections were performed in the sterile operating room, and topical anesthesia was performed with Elcaine eye drops. After disinfection of conjunctival sac with 5% povidone iodine, the injection was administered 3.5 - 4.0mm posterior to the corneal limbus. Approximately 100 microliters of aqueous humor samples were collected from both groups under aseptic conditions. Samples were temporarily stored in liquid nitrogen, and then transferred to a -80\u0026deg;C refrigerator for storage. All injections were performed by the same deputy chief physician at our hospital.\u003c/p\u003e\n\u003cp\u003eMPL\u003c/p\u003e\n\u003cp\u003eThe combined treatment group was treated with MPL 2 weeks after the first injection. The laser with the threshold of 577nm from EASYRET was selected. Using a Volk Area Centralis lens (0.94X), the spot size was set to 160 \u0026micro;m, with an exposure time of 0.2 seconds and a duty cycle of 5%. The power was initially set to 600 mW and gradually increased near the vascular arch for titration test until a newly visible spot appeared, determining the threshold power. 50% of the threshold power adjustment is used as the power parameter of micropulse mode during treatment, and grid-like photocoagulation in macular area is performed and the results are recorded. This laser treatment was conducted by a different deputy chief physician at our hospital.\u003c/p\u003e\n\u003cp\u003eCytokine Measurement Assays\u003c/p\u003e\n\u003cp\u003eFour cytokines in aqueous humor, vascular endothelial growth factor -A(VEGF-A), interleukin-5 (IL-5), monocyte chemoattractant protein -1 (MCP-1) and angiotensin-2 (Ang-2), were quantified using the Luminex platform with the HAGPIMAC kit (Merck, USA). Data were analyzed using the xPONENT Flex Map 3D system, employing a five-parameter curve fitting algorithm with Milliplex Analyst 6.1 software.\u003c/p\u003e\n\u003cp\u003eStatistical Analysis\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eData analysis was conducted using SPSS 26.0., and continuous variables were compared using independent sample T-tests, while categorical data, such as gender and eye type, were analyzed with rank sum tests. BCVA was measured with standard logarithmic visual acuity chart, which was converted into the logarithm of the minimum resolution angle (LogMar). CMT was defined as the distance from the retinal internal limiting membrane to the pigment epithelium at the fovea. The cross-sectional image of macular area is scanned and drawn by OCT, and TMV was calculated using RTVue software based on cross-sectional OCT images of the macular area. Normally distributed variables are summarized by mean and standard deviation, while non-normally distributed variables are presented as median and interquartile range. A repeated measures ANOVA was used to compare BCVA, CMT, TMV, and cytokine concentrations between the two groups before and after treatment, as well as prior to each of the three injections. Statistical significance was set at an \u0026alpha; level of 0.05, with P \u0026lt; 0.05 indicating significance.\u003c/p\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003ePatient characteristics\u003c/h2\u003e \u003cp\u003eA total of 52 patients (52 eyes) participated in this study. The monotherapy group included 27 patients (10 males and 17 females; 15 right eyes and 12 left eyes), with a mean age of 67.74\u0026thinsp;\u0026plusmn;\u0026thinsp;9.24 years. The combination treatment group consisted of 25 patients (12 males and 13 females; 14 right eyes and 11 left eyes) with an average age of 71.64\u0026thinsp;\u0026plusmn;\u0026thinsp;8.89 years. There were no statistically significant differences between the groups in terms of age (P\u0026thinsp;=\u0026thinsp;0.128), gender (P\u0026thinsp;=\u0026thinsp;0.429), or laterality (P\u0026thinsp;=\u0026thinsp;0.975), as detailed in 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\u003ePatient characteristics of the study population\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"6\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eConbercept group\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eCombination treatment group\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cem\u003eZ/t\u003c/em\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u003cem\u003eP\u003c/em\u003e\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eGender\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003emale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e\u0026minus;0.792\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e0.429\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003efemale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e17\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e13\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eEyes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eOD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e14\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e\u0026minus;0.032\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e0.975\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eOS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e11\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eAge (ys)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e67.74\u0026thinsp;\u0026plusmn;\u0026thinsp;9.24\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e71.64\u0026thinsp;\u0026plusmn;\u0026thinsp;8.89\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026minus;1.548\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.128\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eTherapeutic efficacy\u003c/h3\u003e\n\u003cp\u003eBoth treatment groups demonstrated improved visual acuity post-treatment, with the combined treatment group exhibiting better outcomes compared to the conbercept monotherapy group at the first month (t\u0026thinsp;=\u0026thinsp;2.811,p\u0026thinsp;=\u0026thinsp;0.028), the second month (t\u0026thinsp;=\u0026thinsp;3.085,p\u0026thinsp;=\u0026thinsp;0.013) and the third month (t\u0026thinsp;=\u0026thinsp;2.879,p\u0026thinsp;=\u0026thinsp;0.024),as shown in Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e and Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. CMT decreased significantly in both groups after treatment. and the CMT in the combined treatment group was lower than that in conbercept group in the first month (t\u0026thinsp;=\u0026thinsp;2.837,p\u0026thinsp;=\u0026thinsp;0.026), the second month (t\u0026thinsp;=\u0026thinsp;2.925,p\u0026thinsp;=\u0026thinsp;0.021) and the third month (t\u0026thinsp;=\u0026thinsp;2.966, p\u0026thinsp;=\u0026thinsp;0.018),as shown in Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e and Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e. TMV also improved in both groups; however, the TMV in the combination treatment group was significantly lower than that in the conbercept group at the second month (F\u0026thinsp;=\u0026thinsp;2.729, P\u0026thinsp;\u0026lt;\u0026thinsp;0.05) and the third month (F\u0026thinsp;=\u0026thinsp;2.973, P\u0026thinsp;\u0026lt;\u0026thinsp;0.05), In contrast, no statistically significant difference was observed between the two groups in the first month (F\u0026thinsp;=\u0026thinsp;2.485, P\u0026thinsp;=\u0026thinsp;0.065; P\u0026thinsp;\u0026gt;\u0026thinsp;0.05),as shown in Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e and Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\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\u003eComparison of BCVA (Logmar) at different time points in the two groups\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eConbercept group (n\u0026thinsp;=\u0026thinsp;27)\u003c/p\u003e \u003cp\u003e(mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eCombined treatment group (n\u0026thinsp;=\u0026thinsp;25)\u003c/p\u003e \u003cp\u003e(mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003et\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eP value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBase line\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.791\u0026thinsp;\u0026plusmn;\u0026thinsp;0.175\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.752\u0026thinsp;\u0026plusmn;\u0026thinsp;0.272\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.937\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.825\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFirst month\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.498\u0026thinsp;\u0026plusmn;\u0026thinsp;0.134\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.399\u0026thinsp;\u0026plusmn;\u0026thinsp;0.107\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2.811\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.028\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSecond month\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.454\u0026thinsp;\u0026plusmn;\u0026thinsp;0.127\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.353\u0026thinsp;\u0026plusmn;\u0026thinsp;0.103\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3.085\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.013\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eThird month\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.392\u0026thinsp;\u0026plusmn;\u0026thinsp;0.130\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.301\u0026thinsp;\u0026plusmn;\u0026thinsp;0.089\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2.879\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.024\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e\u003cp\u003e(Note: *refers to the comparison between the two groups, the difference is statistically significant (P\u0026thinsp;\u0026lt;\u0026thinsp;0.05))\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 (\u0026micro;m) at different time points in the two groups\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eConbercept group (n\u0026thinsp;=\u0026thinsp;27)\u003c/p\u003e \u003cp\u003e(mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eCombined treatment group (n\u0026thinsp;=\u0026thinsp;25)\u003c/p\u003e \u003cp\u003e(mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003et\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eP value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBase line\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e394.196\u0026thinsp;\u0026plusmn;\u0026thinsp;70.017\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e408.160\u0026thinsp;\u0026plusmn;\u0026thinsp;71.828\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.704\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.930\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFirst month\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e353.556\u0026thinsp;\u0026plusmn;\u0026thinsp;62.702\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e308.400\u0026thinsp;\u0026plusmn;\u0026thinsp;51.890\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2.837\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.026\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSecond month\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e322.148\u0026thinsp;\u0026plusmn;\u0026thinsp;61.815\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e179.920\u0026thinsp;\u0026plusmn;\u0026thinsp;40.887\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2.925\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.021\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eThird month\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e287.778\u0026thinsp;\u0026plusmn;\u0026thinsp;49.427\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e250.120\u0026thinsp;\u0026plusmn;\u0026thinsp;42.033\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2.966\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.018\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \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\u003eTMV at different time points in the two groups (mm\u003csup\u003e\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u003c/sup\u003e) The situation of the comparison\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eConbercept group (n\u0026thinsp;=\u0026thinsp;27)\u003c/p\u003e \u003cp\u003e(mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eCombined treatment group(n\u0026thinsp;=\u0026thinsp;25)\u003c/p\u003e \u003cp\u003e(mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eF\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eP value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBase line\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e10.090\u0026thinsp;\u0026plusmn;\u0026thinsp;1.887\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e10.290\u0026thinsp;\u0026plusmn;\u0026thinsp;1.840\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.385\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.9921\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFirst month\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e9.846\u0026plusmn;\u0026thinsp;1.680\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8.870\u0026thinsp;\u0026plusmn;\u0026thinsp;1.114\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2.485\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.0651\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSecond month\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e9.367\u0026thinsp;\u0026plusmn;\u0026thinsp;1.411\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8.455\u0026thinsp;\u0026plusmn;\u0026thinsp;0.973\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2.729\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.035\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eThird month\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e8.800\u0026thinsp;\u0026plusmn;\u0026thinsp;1.022\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7.994\u0026thinsp;\u0026plusmn;\u0026thinsp;0.959\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2.937\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.020\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eCorrelation between cytokines in aqueous humor and clinical outcomes\u003c/h2\u003e\u003cp\u003eThe concentrations of cytokines were measured in the first and second months, and differences in BCVA, CMT, and TMV from baseline were analyzed to explore the correlations between cytokine levels in aqueous humor and these clinical outcomes. In the first month, The difference of VEGF-A was positively correlated with BCVA, CMT and TMV (r\u0026thinsp;=\u0026thinsp;0.875, 0.457, 0.475, respectively). The difference of IL-5 was positively correlated with the change of CMT and TMV (r\u0026thinsp;=\u0026thinsp;0.380, 0.454, respectively), but did not correlate significantly with BCVA (P\u0026thinsp;\u0026gt;\u0026thinsp;0.05). MCP-1 exhibited a positive correlation with BCVA, TMV and CMT (r\u0026thinsp;=\u0026thinsp;0.449, 0.728, 0.742, respectively). Conversely, the difference in Ang-2 concentration was negatively correlated with the change in BCVA (r = -0.288), but did not show significant correlation with changes in CMT and TMV (P\u0026thinsp;\u0026gt;\u0026thinsp;0.05),as detailed in Table\u0026nbsp;\u003cspan refid=\"Tab5\" class=\"InternalRef\"\u003e5\u003c/span\u003e. In the second month, the change in VEGF-A remained positively correlated with changes in BCVA, CMT, and TMV (r\u0026thinsp;=\u0026thinsp;0.854, 0.541, and 0.718, respectively). The change in IL-5 was also positively correlated with BCVA, CMT, and TMV (r\u0026thinsp;=\u0026thinsp;0.413), while MCP-1 showed positive correlations with BCVA and CMT (r\u0026thinsp;=\u0026thinsp;0.670 and 0.694, respectively). However, the change in Ang-2 was not significantly correlated with BCVA, CMT, or TMV (P\u0026thinsp;\u0026gt;\u0026thinsp;0.05),as detailed in Table\u0026nbsp;\u003cspan refid=\"Tab6\" class=\"InternalRef\"\u003e6\u003c/span\u003e.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab5\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 5\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eCorrelation analysis between cytokine concentration difference and BCVA, CMT and TMV at the first month\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"7\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eCytokine mass concentration difference\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003eBCVA change value\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003eCMT change value\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c7\" namest=\"c6\"\u003e \u003cp\u003eTMV change value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003er\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eP value\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003er\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eP value\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003er\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003eP value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVEGF-A\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.875\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u0026lt;0.001\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.457\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.001\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.475\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u0026lt;0.001\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIL\u0026minus;5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.218\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.121\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.380\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.005\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.454\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.001\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMCP\u0026minus;1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.449\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.001\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.728\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;0.001\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.742\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u0026lt;0.001\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAng\u0026minus;2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u0026minus;0.288\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.038\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026minus;0.034\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.813\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u0026minus;0.026\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.085\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"7\"\u003e(a:Spearman rank correlation analysis)\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab6\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 6\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eCorrelation analysis between cytokine concentration difference and BCVA, CMT and TMV at the second month\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"7\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eCytokine mass concentration difference\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003eBCVA change value\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003eCMT change values\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c7\" namest=\"c6\"\u003e \u003cp\u003eTMV change values\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003er\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eP value\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003er\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eP value\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003er\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003eP value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVEGF-A\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.854\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u0026lt;0.001\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.541\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;0.001\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.718\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u0026lt;0.001\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIL\u0026minus;5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.413\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u0026lt;0.001\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.293\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.035\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.485\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u0026lt;0.001\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMCP\u0026minus;1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.670\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u0026lt;0.001\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.694\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;0.001\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.470\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u0026lt;0.001\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAng\u0026minus;2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u0026minus;0.110\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.437\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026minus;0.014\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.923\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u0026minus;0.085\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.550\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"7\"\u003e(a:Spearman rank correlation analysis)\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eConbercept is a fusion protein anti-VEGF drug that targets all VEGF-A isoforms, placental growth factor and VEGF-B, and has the effects of reducing vascular permeability and tissue vasodilation\u003csup\u003e10\u003c/sup\u003e. The landmark AURORA study\u003csup\u003e11\u003c/sup\u003e showed that 0.5 and 2.0 mg Conbercept could effectively reduce macular edema and improved the visual and anatomical outcomes for PCV patients. However, while beneficial, conbercept does not address the underlying etiology of PCV, leading to high recurrence rates and necessitating repeated injections. Persistent dysfunction of retinal pigment epithelial cells and photoreceptor damage remain significant contributors to central vision loss in these patients.\u003c/p\u003e\n\u003cp\u003eIn the 1990s, Pankratov introduced the MPL mode, and used the sub-domain reaction energy to treat fundus lesions, which can selectively act on retinal pigment epithelial cells, and normal retinal pigment epithelial cells will regenerate to repair the damaged areas and restore the retinal barrier, suggested that it could be an effective choice for PCV treatment\u003csup\u003e12\u003c/sup\u003e. MPL is a kind of short and high-frequency repetitive pulse laser, which includes a series of tiny and repeatable \u0026quot;on-off\u0026quot; pulses in a complete laser exposure process. The single pulse time t includes the action time ON and the intermittent time OFF. The ratio of the ON time and the total exposure time (ON/OFF) is called duty cycle (DC), which represents the effective laser transmission time and can be adjusted independently to realize the fine control of photothermal effect and effective space limitation\u003csup\u003e13\u003c/sup\u003e. During the laser action time, RPE cells absorb the laser and convert the laser light energy into heat energy. During the intermittent time, RPE cells diffuse the absorbed heat energy locally. The spread of heat energy is related to the pulse time. The shorter the laser time, the closer the heat propagation distance, and the less damage to the surrounding tissues. The main action range of MPL is limited to RPE cells, with little damage to the adjacent tissues, and there is no visible laser spot on the retina in the treatment area\u003csup\u003e14,15\u003c/sup\u003e. The subthreshold energy provided by MPL stimulates the production of heat shock proteins (HSPs), which are ubiquitous and highly conserved molecules, and protect cells from any kind of stress by blocking apoptosis and inflammatory pathways that lead to cell damage\u003csup\u003e16\u003c/sup\u003e. In addition, compared with traditional photocoagulation, MPL can also protect color vision and maintain retinal contrast sensitivity\u003csup\u003e17\u003c/sup\u003e. Iovino\u003csup\u003e18\u003c/sup\u003e and other studies have confirmed that MPL therapy can absorb subretinal fluid in central serous chorioretinopathy and retinal fluid in various diseases. As a new non-invasive and effective treatment method, MPL therapy is a cheap and safe treatment method with no adverse reactions to patients. It has a high curative effect in the treatment of subretinal fluid and can be used as the first-line treatment in clinic\u003csup\u003e19\u003c/sup\u003e.\u003c/p\u003e\n\u003cp\u003eOur study demonstrated that after three months of treatment, both groups\u0026mdash;conbercept monotherapy and conbercept combined with MPL\u0026nbsp;showed significant improvement in BCVA, with the combined treatment group achieving superior visual acuity outcomes compared to the monotherapy group.\u0026nbsp;Conbercept could rapidly alleviated disease severity, while subsequent MPL treatment provided biological modulation, enhancing therapeutic effects. CMT and TMV, essential markers reflecting subretinal fluid absorption, were used to quantitatively assess retinal morphology changes through OCT before and after conbercept injection. Both treatment approaches reduced CMT and TMV, with the combined treatment showing a more pronounced clinical benefit. This effect may stem from effect of conbercept on reducing macular edema, while MPL, with its selective and controlled pulse sequences, targets the pathological tissue over a sustained period. The synergy between conbercept and MPL thus enhances the therapeutic impact, indicating that conbercept combined with MPL is an effective approach for treating PCV.\u003c/p\u003e\n\u003cp\u003eThe results showed\u0026nbsp;that VEGF-A, IL-5, MCP-1 and Ang-2 decreased gradually following treatment, and the changes of VEGF-A and MCP-1 were positively correlated with the changes of BCVA, CMT and TMV in the first month and the second month. Many studies have confirmed that VEGF-A was the key pathogenic factor of wet age-related macular degeneration (nAMD) and PCV, with the reduction of VEGF-A concentrations being a primary treatment target in these conditions\u003csup\u003e20-22\u003c/sup\u003e. Researchers also highlights that inflammatory cytokines such as IL-23, MCP-1, VEGF and TNF-\u0026alpha; are related to the pathogenesis of PCV\u003csup\u003e23-26\u003c/sup\u003e. Zhang\u003csup\u003e27\u003c/sup\u003eand colleagues found triamcinolone acetonide more effective than anti-VEGF agents in treating \u0026nbsp;PCV with hemorrhagic retinal detachment, reinforcing the association between PCV and inflammatory cytokines. Our results also fully showed that PCV was not only a neovascular proliferative disease, but also may involved inflammatory factors or other factors. Consequently, the combined anti-VEGF and MPL approach provided a better therapeutic effect for PCV patients compared to anti-VEGF monotherapy, emphasizing the multifactorial nature of PCV and the potential advantages of a multi-modal treatment strategy.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;MCP-1 (monocyte chemoattractant protein -1), also known as chemokine (CC motif) ligand 2(CCL2), is a member of the CC chemokine family and plays a crucial role in the inflammatory response by attracting inflammatory cells, leading to the progression of various diseases through mechanisms involving the migration and infiltration of monocytes, macrophages, and other cells\u003csup\u003e28-30\u003c/sup\u003e. Agawa\u003csup\u003e31\u003c/sup\u003e, Hu\u003csup\u003e32\u003c/sup\u003e and Sakamoto\u003csup\u003e33\u003c/sup\u003e found that the levels of MCP-1 and IP-10 in aqueous humor of PCV patients were higher, while Kato3\u003csup\u003e4\u0026nbsp;\u003c/sup\u003efound that MCP-1 and C3a were significantly higher in PCV and nAMD than in the control group. MCP-1 has chemotactic activity on monocytes and basophils, participates in angiogenesis by stimulating macrophages and RPE, and mediates the increase of VEGF production, which may plays a key role in the development of CNV in PCV\u003csup\u003e35\u003c/sup\u003e. Sun and colleagues\u003csup\u003e36\u003c/sup\u003e indicated that various cytokines, including MCP-1, are related to central macular thickness (CMT) before and after treatment with rezumab in PCV patients, suggesting that both angiogenic and inflammatory factors drive angiogenesis in PCV. The results of our study showed that the change of MCP-1 concentration was positively correlated with BCVA, CMT and TMV, suggesting that MCP-1 may serve as a predictor of visual improvement and retinal morphological changes in PCV patients following anti-VEGF treatment, which could be significant for evaluating prognosis in PCV management.\u003c/p\u003e\n\u003cp\u003eTo sum up, with the development of population aging, the prevalence of PCV is on the rise, presenting ongoing challenges in clinical diagnosis and management. To explore the etiology and pathogenesis of PCV, Improving the understanding of diagnosis and treatment of PCV will help to improve the diagnosis rate of PCV, help to comprehensively judge the prognosis of patients with PCV and adopt personalized treatment, and provide guidance for saving the vision of patients with PCV. Anti-VEGF combined with MPL therapy is more effective than simple anti-VEGF drugs in enhancing vision, reducing CRT, decreasing TMV area, with a high safety profile. Our findings highlight a promising direction for clinical PCV management with notable potential for broader application. However, the study\u0026apos;s limited sample size and short three-month follow-up period warrant further research to evaluate the long-term efficacy of this combined approach.\u003c/p\u003e"},{"header":"Declarations","content":"\u003ch2\u003eEthical Approval\u003c/h2\u003e\n\u003cp\u003eThe studies involving human participants were reviewed and approved by Ethical Committee of Anhui NO.2 Provincial People\u0026rsquo;s hospital ((R)2022-012). The patients/participants provided their written informed consent to participate in this study and agreed to publish the results.\u003c/p\u003e\n\u003ch2\u003eFunding\u003c/h2\u003e\n\u003cp\u003eThis work was supported by Foreign Expert Project of Anhui Provincial Science and Technology Department (S202234017) and Tianjin Health Research Project (TJWJ2024QN026)\u003c/p\u003e\n\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\n\u003cp\u003eShao collected aqueous humor samples.Xue was in charge of micropulse laser therapy.Yin and Ma are collected clinical patient information.Liu and Lu wrote the main manuscript textSun was in charge of the statistical processing of data.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eCheung CMG, Lai TYY, Teo K, Ruamviboonsuk P, Chen SJ, Kim JE, Gomi F, Koh AH, Kokame G, Jordan-Yu JM, Corvi F, Invernizzi A, Ogura Y, Tan C, Mitchell P, Gupta V, Chhablani J, Chakravarthy U, Sadda SR, Wong TY, Staurenghi G, Lee WK (2021) Polypoidal Choroidal Vasculopathy: Consensus Nomenclature and Non-Indocyanine Green Angiograph Diagnostic Criteria from the Asia-Pacific Ocular Imaging Society PCV Workgroup. 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Am J Transl Res 14(10):7147\u0026ndash;7155\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"lasers-in-medical-science","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"lims","sideBox":"Learn more about [Lasers in Medical Science](https://link.springer.com/journal/10103)","snPcode":"10103","submissionUrl":"https://submission.springernature.com/new-submission/10103/3","title":"Lasers in Medical Science","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"conbercept, micropulse laser, polypoidal choroidal vasculopathy, cytokinine, best corrected visual acuity, central macular thickness, total macular volume, monocyte chemotactic protein-1","lastPublishedDoi":"10.21203/rs.3.rs-5290451/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-5290451/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eObjective\u003c/h2\u003e \u003cp\u003eTo evaluate the clinical efficacy of conbercept combined with micropulse laser(MPL) in treating polypoidal choroidal vasculopathy (PCV).\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eIn this prospective, randomized controlled trial conducted from February 2023 to April 2024, 52 patients (52eyes) with PCV at ### hospital were enrolled. Participants were randomized into a conbercept monotherapy group (27cases, 27eyes) and a combination treatment group (conbercept plus micropulse laser(MPL); 25cases, 25eyes). After an initial series of three intravitreal injections, all patients followed the Treat \u0026amp; Extend (T\u0026amp;E) protocol. Aqueous humor samples were collected before each of the first three injections, and cytokines levels were measured after the sample collection. The combined treatment group received a 577nm MPL application two weeks following the first injection. The best corrected visual acuity (BCVA) 、central macular thickness (CMT) and total macular volume (TMV) of each group were assessed monthly for three months.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eFrom the first to the third month post-injection, both treatment groups showed improvements in BCVA and reductions in CMT and TMV, with the combined treatment group demonstrating significantly greater improvements at each monthly evaluation (P\u0026thinsp;\u0026lt;\u0026thinsp;0.05). Additionally, levels of aqueous humor cytokines, including VEGF-A, IL-5, MCP-1, and Ang-2, were significantly reduced in both groups. Reductions in VEGF-A and MCP-1 concentrations were positively correlated with improvements in BCVA, CMT, and TMV (P\u0026thinsp;\u0026lt;\u0026thinsp;0.01).\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eConbercept combined with MPL therapy demonstrates superior clinical efficacy compared to intravitreal injection of Conbercept alone in patients with PCV. Furthermore, changes in VEGF-A and MCP-1 levels may serve as predictive markers for improvements in visual acuity and retinal morphology in these patients.\u003c/p\u003e","manuscriptTitle":"Clinical efficacy of conbercept combined with micropulse laser in patients with polypoidal choroidal vasculopathy","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-10-28 06:52:51","doi":"10.21203/rs.3.rs-5290451/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2025-06-04T21:57:35+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-06-04T06:18:39+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"272388034340349684962615743434479644537","date":"2025-05-09T01:11:10+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-11-08T23:29:03+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"178724024606837241644281902104956761007","date":"2024-11-08T10:12:33+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2024-11-05T23:55:24+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2024-11-05T23:53:43+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2024-10-24T02:29:20+00:00","index":"","fulltext":""},{"type":"submitted","content":"Lasers in Medical Science","date":"2024-10-18T15:15:02+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"lasers-in-medical-science","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"lims","sideBox":"Learn more about [Lasers in Medical Science](https://link.springer.com/journal/10103)","snPcode":"10103","submissionUrl":"https://submission.springernature.com/new-submission/10103/3","title":"Lasers in Medical Science","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"26213da1-04fb-4419-aaa3-5528018f39b9","owner":[],"postedDate":"October 28th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2025-09-29T16:03:45+00:00","versionOfRecord":{"articleIdentity":"rs-5290451","link":"https://doi.org/10.1007/s10103-025-04619-0","journal":{"identity":"lasers-in-medical-science","isVorOnly":false,"title":"Lasers in Medical Science"},"publishedOn":"2025-09-22 15:57:54","publishedOnDateReadable":"September 22nd, 2025"},"versionCreatedAt":"2024-10-28 06:52:51","video":"","vorDoi":"10.1007/s10103-025-04619-0","vorDoiUrl":"https://doi.org/10.1007/s10103-025-04619-0","workflowStages":[]},"version":"v1","identity":"rs-5290451","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-5290451","identity":"rs-5290451","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}