observation on the efficacy of α-lipoic acid capsules combined with conbercept intravitreal injection in the treatment of diabetic macular edema

observation on the efficacy of α-lipoic acid capsules combined with conbercept intravitreal injection in the treatment of diabetic macular edema | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article observation on the efficacy of α-lipoic acid capsules combined with conbercept intravitreal injection in the treatment of diabetic macular edema Jie Wang, Aolin Han, Lingchao Zhang, Yuanqing Liu, Shuting Li, and 2 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7047976/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 6 You are reading this latest preprint version Abstract Objective To investigate the safety and efficacy of α-lipoic acid capsules combined with conbercept intravitreal injection in the treatment of diabetic macular edema. Methods A total of 123 patients with 123 eyes diagnosed with diabetic macular edema who visited our hospital from January 2023 to December 2023 were included in this study. Patients were divided into three groups based on treatment regimens: a placebo control group (n=37), a conbercept intravitreal injection group (IVC) (n=42), and a conbercept intravitreal injection combined with α-lipoic acid capsule treatment group (n=44). All patients in each group were followed up for 12 months, and changes in biological indicators such as best-corrected visual acuity (BCVA), central foveal thickness (CFT), microaneurysm (MA) count, superoxide dismutase (SOD) content in aqueous humor, ganglion cell layer (GCL) thickness, hard exudate (HE) area, and hemorrhage area were compared before and after treatment. Results In the IVC group and the combination therapy group, BCVA, CFT, and MA count showed significant improvements at 6 and 12 months post-treatment compared to pre-treatment levels (P 0.05). The levels of superoxide dismutase (SOD) in the combined treatment group significantly increased at 6 and 12 months post-treatment compared to pre-treatment levels (P 0.05); the thickness of the ganglion cell layer in all three groups showed no significant improvement at 6 months and 12 months post-treatment compared to pre-treatment levels (P > 0.05); the area of hard exudates in all three groups improved at 6 months and 12 months post-treatment compared to pre-treatment levels, with statistically significant differences observed in the IVC group and combined therapy group compared to pre-treatment levels (P < 0.05); the hemorrhage area in all three groups improved at 6 and 12 months post-treatment compared to pre-treatment levels, with statistically significant differences observed (P < 0.05). Conclusion In addition to significantly improving visual acuity, reducing foveal thickness, decreasing the number of microaneurysms, and reducing hemorrhagic and hard exudative areas, the addition of α-lipoic acid capsules to conbercept therapy in patients with DME enhances overall efficacy and increases SOD levels in the aqueous humor, making it worthy of clinical application. α-lipoic acid capsules diabetic macular edema conbercept endothelial growth factor neovascularization 0 Introduction Diabetic retinopathy (DR) is a long-term complication resulting from damage to the retinal blood vessels due to elevated blood sugar levels. As DR advances, patients may experience nonproliferative DR, which is marked by microaneurysms, hemorrhages, hard exudates, and cotton wool spots, or proliferative DR, which involves neovascularization, vitreous hemorrhage, fibrous proliferation, and tractional retinal detachment. Diabetic macular edema (DME) is a potential outcome of DR and can arise at any stage of the condition. Research indicates that around 20% of individuals with type 1 diabetes and 14% to 25% of those with type 2 diabetes develop DME over a 10-year period. The mechanisms behind DME are complex and not fully understood, but current studies suggest that vascular endothelial growth factor (VEGF) contributes to the progression of the disease by promoting the proliferation of vascular endothelial cells and increasing vascular permeability, which disrupts the blood-retinal barrier. This leads to fluid accumulation in the outer plexiform layer and inner nuclear layer of the retina, resulting in retinal thickening and edema in the macular area. Additionally, oxidative stress significantly influences the onset and progression of DME. In patients with DR, several pathways, including the polyol pathway, hexosamine pathway, protein kinase C, angiotensin II, and advanced glycation end products (AGEs), become activated, resulting in the production of excessive reactive oxygen species (ROS) and an imbalance between oxidative and antioxidant defenses.Currently, anti-VEGF medications like conbercept are frequently used to treat DME, although opinions on their effectiveness in clinical settings vary. Alpha-lipoic acid, a natural antioxidant, can neutralize various reactive oxygen species and free radicals in the body, potentially lowering VEGF levels. Combining alpha-lipoic acid with conbercept may improve treatment outcomes. However, there is a lack of clear experimental studies examining the clinical effectiveness of this combination. Therefore, our project aims to investigate the clinical efficacy of α-lipoic acid capsules in conjunction with conbercept intravitreal injections for treating patients with diabetic macular edema, with the intention of providing valuable insights for clinical practice. The findings are detailed below. 1 Data and Methods 1.1 General Information A total of 123 patients (123 eyes) diagnosed with diabetic macular edema who visited our hospital between January 2023 and December 2023 were included in this study. They were divided into three groups based on different treatment regimens: the placebo control group (n=37), the conbercept intravitreal injection group (IVC) (n=42), the conbercept vitreous cavity injection combined with alpha-lipoic acid capsule treatment group (n=44). There were no statistically significant differences in general characteristics among the three groups (P>0.05). This study was approved by the hospital ethics committee, and all patients and their families provided informed consent and signed informed consent forms. Inclusion criteria: (1) Clinically diagnosed with type 2 diabetes mellitus with a clear medical history. (2) Diagnosed with macular edema via slit-lamp examination, optical coherence tomography (OCT), fundus fluorescein angiography (FA), or scanning laser ophthalmoscopy (SLO), with central retinal thickness (CRT) in the macular region exceeding 250 μm, and no scarring or proliferative tissue. (3) Unilateral onset. (4) Good mental status, able to cooperate with relevant examinations and treatments; able to tolerate the treatment regimen of this study; signed informed consent form. Exclusion criteria: (1) Macular edema caused by other diseases. (2) Contraindications to the drugs used in this study. (3) Concurrent other retinal diseases such as retinal vein occlusion, age-related macular degeneration, severe glaucoma, and cataracts. (4) Patients who have recently received anti-vascular endothelial growth factor (VEGF) therapy or retinal laser therapy. (5) Patients with refractive media opacity or poor compliance affecting imaging clarity. (6) Patients unable to cooperate with the study. 1.2 Treatment Methods (1) Patients in the control group will undergo panretinal photocoagulation (PRP) in multiple sessions over one month. One hour before surgery, compound tropicamide eye drops were used for pupil dilation, and five minutes before surgery, ophthalmic lidocaine hydrochloride eye drops were used for anesthesia. The ZEISS laser ophthalmic treatment instrument was used, and photocoagulation was performed using the Goldmann three-mirror system. The photocoagulation area extended 1 PD above and below the optic disc and 1 PD nasally, and from 1–2 PD temporally of the macula to the equator. The parameters were set as follows: Energy: 200–500 mW; laser spot diameter: 200–300 μm; power: 100–200 mW; treatment time: 0.2–0.3 s. (2) Conbercept intravitreal injection (IVC) group: Patients received one IVC (0.5 mg) treatment one week prior to PRP, with PRP initiated one week after injection and completed in multiple sessions within one month. Drug injection was administered using a 3+PRN regimen: one vitreous cavity injection per month (28 days ± 7 days) for the first three months, followed by injections as needed based on follow-up results after three months. During injection, patients were positioned supine, the affected eye was disinfected, and topical anesthesia was administered. A surgical eye shield was applied, and the eyelids were held open using an eyelid retractor. the conjunctival sac is disinfected with povidone-iodine, and the conjunctival sac is rinsed with 0.9% sodium chloride injection. The sclera is vertically punctured from the ciliary body flat area 4.0 mm from the corneal margin to enter the vitreous cavity, and 0.05 mL of conbercept injection solution (National Drug Approval Number S20130012) is injected，apply pressure to the injection site for 1 minute, apply tobramycin and dexamethasone eye ointment (National Drug Approval Number HJ20181126) to the affected eye postoperatively, and cover with a sterile eye patch. Concurrently, patients are instructed to use antibiotic eye drops for 3–5 days following injection. (3) In addition to the above, patients in the conbercept vitreous cavity injection combined with α-lipoic acid capsule treatment group receive oral α-lipoic acid capsules (Jiangsu Wanhe Pharmaceutical，National Drug Approval Number H20100158) at a dose of 0.2 g per dose, three times daily. 1.3 Observation indicators Compare changes in biological indicators such as best-corrected visual acuity (BCVA), central foveal thickness (CFT), microaneurysm (MA) count, superoxide dismutase (SOD) content in aqueous humor, ganglion cell layer (GCL) thickness, hard exudate (HE) area, and hemorrhage area before and after treatment among the three groups. (1) Best-corrected visual acuity (BCVA). The ETDRS visual acuity chart was used to measure visual acuity at baseline, 6 months post-treatment, and 12 months post-treatment. For statistical analysis, BCVA was converted to logarithm of minimum angle of resolution (logMAR). (2) Central foveal thickness (CFT): 6 months post-treatment, and 12 months post-treatment, an optical coherence tomography (Zeiss CIRRUS HD-OCT) was used to scan the retina centered on the macular fovea. The vertical distance from the inner limiting membrane of the retinal neuroepithelium to the inner side of the strongly reflective band of the pigment epithelium was measured as CFT, with three repeated measurements averaged as the final result. (3) Microaneurysm (MA) count: Observed using fundus fluorescein angiography (FA). (４) Superoxide dismutase (SOD) content in aqueous humor: Aqueous humor samples were collected from patients at baseline, 6 months post-treatment, and 12 months post-treatment. SOD expression in the aqueous humor was measured using an enzyme-linked immunosorbent assay (ELISA). (5) Ganglion cell layer (GCL) thickness: Scanning was performed using an optical coherence tomography scanner (Zeiss CIRRUS HD-OCT) at baseline, 6 months post-treatment, and 12 months post-treatment. The vertical distance from the inner plexiform layer to the inner side of the nerve fiber layer in the affected eye was measured as the GCL thickness, with three repeated measurements averaged to obtain the final result. (6) Hard exudate (HE) area: Observed using fundus laser scanning imaging technology (Scanning Laser Ophthalmoscope, SLO). (7) Hemorrhage area: Observed using fundus laser scanning imaging (Scanning Laser Ophthalmoscope, SLO). 1.4 Statistical methods The data were analyzed with SPSS 22.0 statistical software. Continuous variables that followed a normal distribution were presented as mean ± standard deviation. To compare different time points within the same group, repeated measures analysis of variance was utilized. Categorical variables were represented as percentages and assessed using the chi-square test. A P value of less than 0.05 was deemed statistically significant. 2 Results 2.1 Comparison of general clinical data between the two groups of patients There were no statistically significant differences in general clinical data such as gender, age, duration of diabetes, and smoking history between the three groups of patients (all P > 0.05, Table 1). Table 1 General information of patients IVC group (n=42) Combined group (n=44) the control group (n=37) t，c2 P Sex Male 22（52.4%） 21（47.7%） 18（48.6%） 0.205 0.9026 Female 20（47.6%） 23（52.3%） 19（51.4%） Age 65.95±4.06 64.66±4.04 64.68±3.50 1.501 0.2273 Onset time (month) 1.87±0.50 1.90±0.45 1.96±0.57 0.323 0.7301 BCVA (logMAR) 0.68±0.0.13 0.71±0.12 0.71±0.13 0.840 0.4350 CFT （mm） 457.35±31.88 453.92±38.63 445.24±32.82 1.261 0.2882 MA 125.46±29.96 121.76±32.35 116.63±29.99 0.812 0.4478 Diabetes history (year) 6.14±1.26 6.02±1.09 6.11±1.51 0.101 0.9075 Smoking history 11(26.2%) 10(22.7%) 8（21.6%） 0.255 0.8801 Number of injection 5.66±1.20 4.45±0.90 - 5.305 0.0000 2.2 Comparison of BCVA Among the Three Groups of Patients at Different Time Points Before treatment, there were no statistically significant differences in BCVA among the three groups. At 12 months post-treatment, there were no significant changes in the placebo control group, while the BCVA (log MAR) in the IVC group and the IVC combined with α-lipoic acid capsule treatment group improved compared to pre-treatment levels, with statistically significant differences (P < 0.05; P < 0.05). At 12 months post-treatment, the differences between the placebo control group and the IVC group, as well as between the placebo control group and the combined treatment group, were statistically significant (P < 0.05; P 0.05). (Table 2) Table 2 Comparison of BCVA before and after treatment between the two groups of patients Pre－ treatment BCVA（logMA） ６months post-treatment BCVA（logM） 12 months post-treatment BCVA（logMAR） F P IVC group (n=42) 0.68±0.0.13 0.42±0.11 0.42±0.12 67.88 0.0000 Combined group (n=44) 0.71±0.12 0.44±0.10 0.40±0.12 101.26 0.0000 the control group (n=37) 0.71±0.13 0.70±0.10 0.69±0.12 0.48 0.6191 F 0.84 85.82 68.47 P 0.4350 0.0000 0.0000 2.3 Comparison of CFT Among the Three Groups of Patients at Different Time Points Before treatment, there were no statistically significant differences in CFT (μm) among the three groups. At 12 months post-treatment, the control group showed no significant changes, while the CFT (μm) in the IVC group and the IVC combined with α-lipoic acid capsule treatment group were both reduced compared to pre-treatment levels, with statistically significant differences (P < 0.05; P < 0.05). At 12 months post-treatment, the differences between the blank control group and the IVC group, as well as between the blank control group and the combined group, were statistically significant (P < 0.05; P 0.05). (Table 3) Table 3 Comparison of CFTs before and after treatment between the two groups of patients Pre－ treatment CFT（mm） ６months post-treatment CFT（mm） 12 months post-treatment CFT（mm） F P IVC group (n=42) 457.35±31.88 291.98±33.74 294.63±35.32 332.27 0.0000 Combined group (n=44) 453.92±38.63 295.35± 33.91 286.65±32.99 313.69 0.0000 the control group （n=37) 445.24±32.82 457.22±32.38 447.25±35.15 1.36 0.2611 F 1.26 310.11 268.20 P 0.2882 0.0000 0.0000 2.4 Comparison of changes in MA counts among the three groups at different time points Before treatment, there were no statistically significant differences in MA counts among the three groups. At 12 months post-treatment, there were no significant changes in the placebo control group, while MA counts in the IVC group and the IVC combined with α-lipoic acid capsule treatment group decreased compared to pre-treatment levels, with statistically significant differences (P < 0.05; P < 0.05). At 12 months post-treatment, the differences between the blank control group and the IVC group, as well as between the blank control group and the combined group, were statistically significant (P < 0.05; P 0.05). (Table 4) Table 4 Comparison of the number of MA before and after treatment in the two groups of patients pre-treatment MA ６ months post-treatment MA 12 months post-treatment MA F P IVC group (n=42) 125.46±29.96 71.59±31.37 66.75±29.83 48.28 0.0000 Combined group (n=44) 121.76±32.35 68.58±28.88 68.03±28.62 46.56 0.0000 the control group (n=37) 116.63±29.99 111.82±28.67 115.30±28.66 0.27 0.7647 F 0.81 25.71 35.17 P 0.4478 0.0000 0.0000 2.5 Comparison of changes in superoxide dismutase (SOD) levels (U/ml) in the aqueous humor of three groups of patients at different time points Before treatment, there were no statistically significant differences in SOD levels in the aqueous humor of the three groups of patients. At 12 months post-treatment, there were no significant changes in SOD levels between the placebo control group and the IVC group, with no statistically significant differences (P > 0.05); however, SOD levels in the IVC combined with α-lipoic acid capsule treatment group showed a significant increase, with statistically significant differences (P < 0.05). (Table 5) Table 5 Comparison of superoxide dismutase (SOD) levels (U/ml) before and after treatment between the two groups of patients pre-treatment SOD（U/ml） 12 months post-treatment SOD（U/ml） 12 months post-treatment SOD（U/ml） F P IVC group (n=42) 315.28±30.86 321.44±31.10 320.56±28.77 0.51 0.6020 Combined group (n=44) 313.67±22.11 375.29±26.77 386.52±29.38 98.13 0.0000 the control group (n=37) 324.75±30.12 317.29±28.94 318.98±30.17 0.64 0.5294 F 1.81 52.67 72.69 P 0.1682 0.0000 0.0000 2.6 Comparison of changes in ganglion cell layer thickness (μm) among the three groups of patients at different time points Before treatment, there were no statistically significant differences in GCL (μm) thickness among the three groups. At 12 months post-treatment, the GCL thickness decreased in the placebo control group, while it increased in the IVC group and the IVC combined with α-lipoic acid capsule treatment group. However, there were no significant changes in GCL thickness before and after treatment in all three groups, and the differences were not statistically significant (P > 0.05). (Table 6) Table 6 Comparison of ganglion cell layer thickness ( μm) before and after treatment between the two groups of patients pre-treatment GCL（mm） ６ months post-treatment GCL（mm） 12 months post-treatment GCL（mm） F P IVC group (n=42) 35.70±7.08 35.85±6.49 36.28±7.37 0.08 0.9252 Combined group (n=44) 37.12±5.19 37.89±6.46 39.55±6.60 1.81 0.1674 the control group (n=37) 36.17±6.40 36.44±5.56 5.17±5.39 0.49 0.6138 F 0.58 1.23 5.01 P 0.5615 0.2950 0.0081 2.7 Comparison of changes in the area of hard exudate (mm²) among the three groups of patients at different time points Before treatment, there were no statistically significant differences in the area of hard exudate (mm²) among the three groups. At 12 months post-treatment, the area of hard exudate improved in all three groups compared to pre-treatment levels. Among these, the IVC group and the IVC combined with α-lipoic acid capsule treatment group showed statistically significant differences compared to pre-treatment levels (P < 0.05). (Table 7) Table7 Comparison of hard exudate area (mm2) before and after treatment between the two groups of patients HE pre-treatment 12 months post-treatment χ 2 P IVC group (n=42) 3.5mm 2 5 7 Combined group (n=44) 3.5mm 2 7 4 the control group (n=37) 3.5mm 2 9 3 χ 2 3.988 11.971 P 0.408 0.018 2.8 Comparison of changes in bleeding area (mm²) among the three groups of patients at different time points Before treatment, there were no statistically significant differences in bleeding area (mm²) among the three groups. At 12 months post-treatment, bleeding area improved in all three groups compared to pre-treatment levels, with statistically significant differences (P < 0.05). (Table 8) Table 8 Comparison of haemorrhage area (mm2) before and after treatment between the two groups of patients haemorrhage area (mm2) pre-treatment 12 months post-treatment χ 2 P IVC group (n=42) 4mm 2 5 1 Combined group (n=44) 4mm 2 13 1 the control group (n= 37) 4mm 2 8 1 χ2 5.3229 10.9740 P 0.2557 0.0269 3 Discussion DM is characterized by an increase in central macular thickness (CMT). In the early stages of the disease, patients may experience symptoms such as blurred vision and visual distortions, which can impair normal daily activities. If not addressed in the advanced stages, there is a significant risk of blindness. These symptoms are closely related to the destructive effects of hyperglycemia on blood vessels, leading to retinal ischemia and hypoxia, which in turn results in increased release of VEGF. VEGF is a disulfide-linked dimeric glycoprotein, belonging to the class of peptide growth factors. It was first isolated and purified from the culture medium of bovine pituitary follicular stellate cells by Ferrara et al. in 1989 ６ .Among the VEGF family, VEGF-A is most abundantly expressed in the ocular vascular system and neovascular tissues, and many ocular vascular proliferative diseases are closely associated with its regulation and expression.⁷ Additionally, hyperglycemia also causes oxidative stress in the body. In patients with diabetic retinopathy (DR), there is an elevation in the levels of oxygen free radicals, lipid peroxides, and malondialdehyde (MDA), whereas the activity of antioxidant defense enzymes that help eliminate free radicals, including superoxide dismutase (SOD), glutathione reductase, glutathione peroxidase, and catalase, is diminished⁸. Typically, the body's oxidative and antioxidant systems maintain a balance. However, when the production of free radicals surpasses the ability of the antioxidant defense system to eliminate them, it leads to a disruption in redox homeostasis. The retina is particularly vulnerable to oxidative stress damage because of its high metabolic activity.Reactive oxygen species (ROS) amplify inflammatory responses by activating the protein kinase C (PKC) pathway or triggering the activation of the central inflammatory mediator nuclear factor-κB (NF-κB), thereby upregulating the expression of vascular endothelial growth factor (VEGF) protein. The current standard treatment for DME involves intravitreal injections of anti-VEGF drugs.¹¹ Conbercept is a domestically produced anti-VEGF drug in China that binds to IgG-Fc fusion proteins in the body to block VEGF signaling. However, such drugs have a short half-life, limited duration of action, and poor specificity.¹²⁻¹³ Frequent intravitreal injections also increase the incidence of endophthalmitis, posing certain safety risks for clinical use. Additionally, the high cost of these drugs results in poor compliance among some patients. Alpha-lipoic acid is a natural antioxidant that helps remove different reactive oxygen species and free radicals from the body. It also binds to metal ions to inhibit the formation of free radicals, enhances the function of endothelial nitric oxide synthase (eNOS), and works together with other antioxidants like glutathione (GSH), vitamin C, and vitamin E to produce combined antioxidant benefits.The antioxidant action of α-lipoic acid is mediated through the stabilization and nuclear translocation of the nuclear factor erythroid 2-related factor 2 (Nrf2)¹⁶, which controls the expression of key genes involved in ROS elimination through the Nrf2 antioxidant response element signaling pathway, such as those encoding SOD and the catalytic subunit of glutathione S-transferase 17 . Nrf2 can also block NF-κB activation, thereby alleviating oxidative stress. Zhang Xinfang et al. found that α-lipoic acid capsules can reduce vascular endothelial damage, inhibit neovascularization, and alleviate symptoms and effectively controlling the condition １８ . In addition to its effects on oxidative stress within the body, α-LA is also believed to play a role in blood glucose control. In a study conducted by Yoon Sook Kim and colleagues, it was observed that in mouse models of diabetes induced by STZ, the control group experienced a notable rise in blood glucose levels, whereas the mice that received α-LA treatment kept their blood glucose levels within the normal range for the duration of the experiment １９ . This study investigated the efficacy of α-lipoic acid capsules combined with conbercept intravitreal injection for the treatment of diabetic macular edema, and compared the results with those of patients who received conbercept intravitreal injection alone. The results showed that the best-corrected visual acuity (BCVA), central foveal thickness (CFT), and number of microaneurysms (MA) improved in all three groups over time. Patients with macular edema have a large number of neovascularization, which, due to their fragility and thin vessel walls, lead to the formation of microaneurysms. Additionally, the high permeability of neovascularization causes excessive fluid leakage and accumulation between retinal layers, resulting in increased CFT. BCVA is a critical functional outcome metric for assessing treatment efficacy. Previously, Li Shuang and colleagues discovered that administering three consecutive intravitreal injections of conbercept for diabetic macular edema (DME) led to a significant decrease in central foveal thickness (CFT), reduced macular edema, and enhanced visual acuity, indicating both effectiveness and safety. The results of this study also showed that after 12 months of treatment, there were no significant changes in the control group, while the BCVA (log MAR) in the conbercept group and the conbercept combined with α-lipoic acid capsule treatment group improved from (0.68 ± 0.13) and (0.71 ± 0.12) to (0.42 ± 0.12) and (0.40 ± 0.12), respectively, with the combined group showing better BCVA than the conbercept treatment group, suggesting that α-lipoic acid can better promote visual recovery in DME patients. The CFT (μm) in both groups decreased from (457.35 ± 31.88) (453.92 ± 38.63) to (294.63 ± 35.32) and (286.65 ± 32.99), respectively, indicating that both conbercept and α-lipoic acid can reduce VEGF, regulate the permeability of the blood-retinal barrier, and alleviate macular edema. This study found that only the group treated with a combination of conbercept and α-lipoic acid capsules showed significant changes in superoxide dismutase (SOD) levels in the aqueous humor, which increased from 313.67 ± 22.11 to 386.52 ± 29.38 U/ml, with a statistically significant difference (P < 0.05). This indicates that, compared to treatment with conbercept alone, α-lipoic acid can reduce oxidative stress-induced damage to the retina by enhancing the expression of SOD.Common indicators of free radical levels in the body include malondialdehyde (MDA) and SOD. MDA reflects oxidative stress levels, while SOD indicates antioxidant defense capacity. In a study by Yu Wenfeng et al., diabetic patients without retinopathy exhibited significantly elevated MDA levels and significantly reduced SOD levels compared to healthy controls. This indicates that individuals with diabetes, even without diabetic retinopathy (DR), experience a significant level of oxidative stress ２１ .In an animal experiment conducted by Zhou Jin et al., the group treated with α-lipoic acid showed decreased MDA levels and increased SOD levels compared to the non-treated diabetic group. Many other studies have also shown that reactive oxygen species (ROS) production increases in bovine retinal endothelial cells or human retinal endothelial cells exposed to high glucose levels ２２ . Incorporating cytoplasmic copper/zinc-dependent SOD into the culture medium can help avert cell death caused by elevated glucose levels. These findings are consistent with the outcomes of this study. Superoxide is the primary reactive species responsible for oxidative stress in diabetes. Research by Kanwar et al. indicated that diabetic mice generated more superoxide in their retinas than normal control mice ２３ . During the secretion of retinal vascular endothelial growth factor (VEGF), the oxidant nitrotyrosine and the nuclear transcription factor NF-kB are crucial players. α-Lipoic acid can reduce the expression of retinal VEGF and limit the formation of new blood vessels by inhibiting the activation of these two oxidants and curbing the excessive production of superoxide radicals. ２４ . In terms of changes in the area of hard exudates (mm²), all three groups showed improvement compared to pre-treatment levels. Hard exudates (HE) in the retina appear as yellowish-white deposits found in the outer plexiform layer, primarily composed of lipids and proteins, indicating damage to capillary endothelial cells. If they occur in the fovea centralis, they can cause significant vision impairment. Studies have shown that treatment with conbercept for PDR resulted in a significant reduction in HE area at each follow-up time point compared to the initial month 25–26 ． , similar to the results of this study. The results of this study show that in the combination therapy group, the area of exudates greater than 3.5 mm², those in the 1.5 mm²–3.5 mm² range decreased, and those less than 1.5 mm² increased, with the most significant changes observed. We speculate that compared to monotherapy with laser or conbercept, α-lipoic acid may have a superior protective effect on retinal capillary endothelial cells. Further analysis of changes in hemorrhage area (mm²) before and after treatment revealed that hemorrhage area improved in all three groups compared to pre-treatment levels.Conbercept significantly reduces VEGF levels by inhibiting its binding to receptors, while α-lipoic acid blocks excessive superoxide formation and inhibits retinal VEGF expression. Both agents inhibit retinal neovascularization and reduce retinal hemorrhage. In terms of changes in ganglion cell layer thickness (μm), domestic studies have used automated full-threshold microperimetry to measure ganglion cell layer thickness and microperimetry changes, finding that a reduction in ganglion cell layer (GCL) thickness is associated with improvements in best-corrected visual acuity (BCVA) and has the best predictive effect on BCVA improvements. This indicates that once macular edema subsides, enhancements in vision, microfield improvements, and neuronal recovery are linked to a decrease in GCL thickness ２７ . Retinal ganglion cells serve as an ideal model for studying new treatment methods for retinal degenerative diseases (particularly diabetic retinopathy), and alpha-lipoic acid can protect ganglion cells and reduce apoptosis ２８ . Animal studies have reported reduced retinal ganglion cell counts in diabetic animals, and the number of RGCs in the retinas of mice treated with alpha-lipoic acid was significantly increased compared to diabetic mice. Alpha-lipoic acid can restore the normal activity of the Na+/K+-ATPase enzyme in the neuronal cell membranes of diabetic rats, increase the production of inositol in the neuronal membranes, and improve neuronal damage ２９ . However, the results of this study showed that after 12 months of treatment, the GCL (μm) in the control group, the conbercept group, and the combined group changed from (36.17 ± 6.40), (35.70 ± 7.08), and (37.12 ± 5.19) to (35.17 ± 5.39), (36.28 ± 7.37), and (39.55 ± 6.60), respectively, with no significant improvement before and after treatment (P > 0.05). We believe that the brief follow-up period could be a reason for not detecting notable changes in the indicators. Additional long-term studies are necessary to better understand the impact of anti-VEGF therapy and α-lipoic acid therapy on the thickness of the retinal ganglion cell layer and the quantity of ganglion cells. In terms of injection frequency, the average number of injections in the conbercept group was 5.66 ± 1.20, which was higher than the 4.45 ± 0.90 in the combination group. This suggests that conbercept treatment for DME may increase the number of injections and patient discomfort, while the combination therapy with alpha-lipoic acid may have advantages in fewer injections, reduced costs, and lower risks related to the injections. Retinal laser photocoagulation therapy also has a certain therapeutic effect on DME patients, but this method can damage ocular tissues and induce complications such as blurred vision and vitreous hemorrhage. Not every DME patient who receives laser therapy sees a decrease in edema, indicating that laser therapy has its constraints³⁰⁻³¹．Based on this, we applied anti-VEGF and α-lipoic acid therapy to patients and compared the efficacy of the two treatment regimens. In summary, at 12 months post-treatment, α-lipoic acid therapy demonstrated significantly superior outcomes compared to conbercept therapy in terms of best-corrected visual acuity (BCVA), hard exudate (HE) area, hemorrhage area, changes in superoxide dismutase (SOD) levels in aqueous humor, and number of injections. However, this study had a small sample size and a short observation period, which is insufficient to conclusively demonstrate the long-term differences in treatment efficacy. Further research involving larger participant groups and extended follow-up times is necessary to determine the long-term effectiveness of α-lipoic acid treatment for diabetic macular edema. This will help in its clinical use to enhance and sustain the visual outcomes for patients with DME over time. Declarations Acknowledgements This study is the culmination of a long and arduous journey. I have only been able to make it due to the dedicated support from Qilu Hospital, Shandong University.My deepest and sincerest gratitude goes to my supervisor Shuting Li , for her continuous and invaluable guidance throughout my research. Funding No funding or sponsorship was received for this study or publication of this article. Author Contributions Conceptualisation: Shuting Li. Formal analysis: Aolin Han. Writing-original draft preparation and editing: Jie Wang. Methodology: Yuanqing Liu，Lingchao Zhang. Validation: Hong Wang, Pengfei Jiang. Disclosures The authors declare that they have no conflict of interest. Compliance with Ethics Guidelines The study was approved by the Ethical Committee of Qilu Hospital of Shandong University (approval no. 2021051). Data Availability The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request. Thanking Patient Participant(s) Thanks for the contributions of all patients and volunteers. Prior Presentation Not applicable. References Li Binbin, Tan Meihua, Yin Zhangliang. Comparison of the efficacy of different dosing regimens of Conbercept in the treatment of clinically significant diabetic macular edema. International Journal of Ophthalmology. 2022;22(1):130-134 Zhang Hanwen, Shi Yan. Advances in Research on the Mechanisms of Diabetic Retinopathy and Blood-Retinal Barrier Damage. Chinese Journal of Retinal Diseases. 2013;29(6):6113-6137 Wan Guangming, Xue Rong. Discussion on the pathogenesis and prevention and treatment strategies of diabetic retinopathy from the perspective of retinal oxidative stress and microvascular changes [J]. Advances in Ophthalmology, 2022, 42(7):505-509 Guo Mi, Bian Hongxia, Bian Mengting, Yao Yanyan, Ma Guomin. Effect of Conbercept Treatment on the Retinal Ellipsoid Zone in Different OCT Subtypes of Diabetic Macular Edema. Journal of Clinical Ophthalmology. 2023, 31(2):121–125. Christine Altmann and Mirko H，H. Schmidt. The Role of Microglia in Diabetic Retinopathy: Inflammation, Microvasculature Defects and Neurodegeneration.Molecular Sciences.2018;19(110):1-31 Xu Shanshan, Zhang Chong. Application and Research Progress of Anti-Vascular Endothelial Growth Factor Drugs in the Treatment of Ophthalmic Diseases. Journal of Clinical Drug Therapy. 2020;18(2):6-11 Xu Juan, Gao Yun, Yue Feng. Effects of α-Lipoic Acid on Vascular Endothelial Growth Factor in Patients with Diabetic Retinopathy. Journal of Taishan Medical College. 2012;33(4):250-251 Sul Gee Lee, Chang Gun Lee，Il Han Yun.Effect of lipoic acid on expression of angiogenic factors in diabetic rat retina. Clinical & Experimental Ophthalmology. 2011;40(1):47-57 Cameron D. Haydinger. Genevieve F. Oliver. Liam M. Ashander. Justine R. Smith.Oxidative Stress and Its Regulation in Diabetic Retinopathy. Antioxidants. 2023；12(8):1-25 Di Sha, Wang Tianchu, Pang Bing, Li Min. Research Progress on the Pathogenesis and Treatment of Diabetic Retinopathy. Medical Review. 2021;27 (21):4285-4291 Xiaolei Sun, Jingjing Zhang, Jingyi Tian, Shijiu Chen, Fanxing Zeng. Comparison of the Efficacy and Safety of Intravitreal Conbercept with Intravitreal Ranibizumab for Treatment of Diabetic Macular Edema: A Meta-Analysis. Journal of Ophthalmology. 2020; 2020:1-8 Wang Zongqing, Liu Xiangling, Zhou Lixiao, Dong Hongtao, Han Xiaodong. Effects of Laser Combined with Alpha-Lipoic Acid on Central Retinal Artery Hemodynamics and Vascular Endothelial Growth Factor in Diabetic Retinopathy. Clinical Medical Engineering. 2019; 26(12):1637-1638 Zhao Yang, Shi Yan. Pathogenesis and treatment progress of diabetic macular edema. Medical Review. 2019;25(17):3463-3472 Bai Mengmeng, Zhang Hui Juan, Mou Jiawei, Xu Wenhui, Zhang Hong. The role of lipoic acid in the treatment of diabetic microvascular complications. Advances in Modern Biomedical Science. 2016;(16)9:1756-1758 Packer L, Kraemer K, Rimbach G (2001) Molecular aspects of lipoic acid in the prevention of diabetes complications. Nutrition 17:888–895 FAYEZ A M, ZAKARIA S, MOUSTAFA D. Alpha lipoic acid exerts antioxidant effect via Nrf2/HO-1 pathway activation and suppresses hepatic stellate cells activation induced by methotrexate in rats[J]. Biomed Pharmacother, 2018,105:428-433. Zhang Fengjun, Li Jingming, Liu Qiuping. Advances in the pathogenesis and potential treatment of diabetic retinopathy [J]. Advances in Ophthalmology, 2020, 40(7): 677-685 Zhang Xinfang, Dong Kaixia. Efficacy of alpha-lipoic acid capsules in the treatment of simple diabetic retinopathy in the elderly. Chinese Journal of Gerontology, 2015;35(15):4357-4358 Yoon Sook Kim, Minjun Kim, Mee Young Choi, Dong Hoon Lee, Gu Seob Roh, Hyun Joon Kim, Sang Soo Kang, Gyeong Jae Cho, Eun-Kyung Hong, Wan Sung Choi. Alpha-lipoic acid reduces retinal cell death in diabetic mice. Biochemical and Biophysical Research Communications. 2018; 503(3): 1307-1314. Li Shuang, Xiang Yi, Mei Zhongming. Efficacy of intravitreal injection of Conbercept for diabetic macular edema. Chinese Journal of Geriatrics. 2019; 39(21): 5198-5201 Yu Wenfeng, Li Mingjie. Expression of inflammatory factors and oxidative stress markers in peripheral blood of patients with diabetic retinopathy. Medical Review. 2018;24(20):4147-4151 Zhou Jin, Ying Changjiang, Li Wei. Protective effect of α-lipoic acid on diabetic retinopathy in rats. Chinese Journal of Geriatrics. 2013;33(22):5667-5669 Kanwar, M.; Chan, P.S.; Kern, T.S.; Kowluru, R.A. Oxidative damage in the retinal mitochondria of diabetic mice: Possible protection by superoxide dismutase. Investig. Ophthalmol. Vis. Sci. 2007, 48, 3805–3811. Kowluru RA, Odenbach S.Effect of long-term administration of alpha-lipoic acid on retinal capillary cell death and the development of retinopathy in diabetic rats. Diabetes .2004.53:3233–3238 Domalpally A, Ip MS, Ehrlich JS. Effects of intravitreal ranibizumab on retinal hard exudate in diabetic macular edema: findings from the RIDE and RISE phase III clinical trials. Ophthalmology. (2015) 122:779–86. Lu Shen，Yuxiang Zheng，Zelan Gao, Qirui Li，Min Dai.Efficacy and safety of intravitreal injection of conbercept for moderate to severe nonproliferative diabetic retinopathy. Frontiers in Medicine. 2024(11):1-8 Yupeng Xu, Yuan Qu, Yan Suo, Jian Gao, Xia Chen, Kun Liu,Xun Xu. Correlation of retinal layer changes with vision gain in diabetic macular edema during conbercept treatment[J]. BMC Ophthalmol, 2019,19(1):123. Lee SG, Lee CG, Yun IH, et al. Effect of lipoic acid on expression of angiogenic factors in diabetic rat retina [J]. Clin Experiment Ophthalmol, 2012, 40(1): 47-57 Emrah Kan . O¨mer Alici . Elif Kılıc¸ Kan . Ahmet Ayar．Effects of alpha-lipoic acid on retinal ganglion cells, retinal thicknesses, and VEGF production in an experimental model of diabetes．International Ophthalmology．2016；6（３７）：1269-1278． Li Wentao, Wang Rui Feng, Tang Wenjian, Gao Xuexia. The effect of combination therapy with Conbercept and laser photocoagulation on patients with diabetic macular edema. Practical Clinical Medicine Combining Chinese and Western Medicine. 2025;25(1):26-29. Weizhe Meng，Ronghua Li，Xiufen Xie.Conbercept and Retinal Photocoagulation in the treatment of Diabetic Macular Edema. Pakistan Journal of Medical Sciences. 2019;35(6):1493-1498. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Under Review Version 1 posted Reviewers agreed at journal 16 Aug, 2025 Reviewers invited by journal 16 Aug, 2025 Editor invited by journal 05 Aug, 2025 Editor assigned by journal 09 Jul, 2025 Submission checks completed at journal 09 Jul, 2025 First submitted to journal 04 Jul, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-7047976","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":501291359,"identity":"9ac7f595-a0e0-4e90-95b6-62f1820c8707","order_by":0,"name":"Jie Wang","email":"","orcid":"","institution":"Qilu Hospital of Shandong Province","correspondingAuthor":false,"prefix":"","firstName":"Jie","middleName":"","lastName":"Wang","suffix":""},{"id":501291360,"identity":"79b8188b-1e72-49f3-bb33-1d37f121544b","order_by":1,"name":"Aolin Han","email":"","orcid":"","institution":"Qilu Hospital of Shandong Province","correspondingAuthor":false,"prefix":"","firstName":"Aolin","middleName":"","lastName":"Han","suffix":""},{"id":501291361,"identity":"3b509dc0-06a3-4c74-be00-ab68a5249824","order_by":2,"name":"Lingchao Zhang","email":"","orcid":"","institution":"Qilu Hospital of Shandong Province","correspondingAuthor":false,"prefix":"","firstName":"Lingchao","middleName":"","lastName":"Zhang","suffix":""},{"id":501291362,"identity":"f2fa61a0-a853-4d09-8700-a88f03f040d9","order_by":3,"name":"Yuanqing Liu","email":"","orcid":"","institution":"Qilu Hospital of Shandong Province","correspondingAuthor":false,"prefix":"","firstName":"Yuanqing","middleName":"","lastName":"Liu","suffix":""},{"id":501291363,"identity":"4821161f-9b5a-409f-9b74-92f1f7c1cc68","order_by":4,"name":"Shuting Li","email":"","orcid":"","institution":"Qilu Hospital of Shandong Province","correspondingAuthor":false,"prefix":"","firstName":"Shuting","middleName":"","lastName":"Li","suffix":""},{"id":501291365,"identity":"0556152f-3d4a-400c-a396-ad9b9cb84933","order_by":5,"name":"Hong Wang","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA2UlEQVRIiWNgGAWjYDCCAxAqAYgZHyRU1JCmhdngwZljpGlhk3zYwkxYB9/tA2wSP3fU5vFLt1+rSGxgY+Bv707Aq0XyXAKbZO+Z48WSc86U3UjcIcMgcebsBrxaDM4wsN3gbTuWuOFGTtqNxDNsDAYSuYS13PwL1VKQ2MZMnJbbvG01QC3pxxiI0iJ5hrH9t2zbgcSZM3KYJRLOHOMh6Be+M8yHDd+21SX2S6Q//PijokaOv70XvxZgnDcAicNAzGMA4vIQUA4HdUDM/oBY1aNgFIyCUTDCAABZ1FBLBL70UgAAAABJRU5ErkJggg==","orcid":"","institution":"Qilu Hospital of Shandong Province","correspondingAuthor":true,"prefix":"","firstName":"Hong","middleName":"","lastName":"Wang","suffix":""},{"id":501291367,"identity":"94e0be2a-d251-46da-afd0-1c12d49f0654","order_by":6,"name":"Pengfei Jiang","email":"","orcid":"","institution":"Yuhuangding Hospital","correspondingAuthor":false,"prefix":"","firstName":"Pengfei","middleName":"","lastName":"Jiang","suffix":""}],"badges":[],"createdAt":"2025-07-04 15:08:17","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-7047976/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-7047976/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":89794220,"identity":"daf8c535-96d8-401c-9aec-458b731ee13b","added_by":"auto","created_at":"2025-08-25 06:40:51","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":696559,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7047976/v1/bcc8806a-b50c-48b7-a971-4825cd9c57c0.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"observation on the efficacy of α-lipoic acid capsules combined with conbercept intravitreal injection in the treatment of diabetic macular edema","fulltext":[{"header":"0 Introduction","content":"\u003cp\u003eDiabetic retinopathy (DR) is a long-term complication resulting from damage to the retinal blood vessels due to elevated blood sugar levels. As DR advances, patients may experience nonproliferative DR, which is marked by microaneurysms, hemorrhages, hard exudates, and cotton wool spots, or proliferative DR, which involves neovascularization, vitreous hemorrhage, fibrous proliferation, and tractional retinal detachment. Diabetic macular edema (DME) is a potential outcome of DR and can arise at any stage of the condition. Research indicates that around 20% of individuals with type 1 diabetes and 14% to 25% of those with type 2 diabetes develop DME over a 10-year period.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe mechanisms behind DME are complex and not fully understood, but current studies suggest that vascular endothelial growth factor (VEGF) contributes to the progression of the disease by promoting the proliferation of vascular endothelial cells and increasing vascular permeability, which disrupts the blood-retinal barrier. This leads to fluid accumulation in the outer plexiform layer and inner nuclear layer of the retina, resulting in retinal thickening and edema in the macular area. Additionally, oxidative stress significantly influences the onset and progression of DME. In patients with DR, several pathways, including the polyol pathway, hexosamine pathway, protein kinase C, angiotensin II, and advanced glycation end products (AGEs), become activated, resulting in the production of excessive reactive oxygen species (ROS) and an imbalance between oxidative and antioxidant defenses.Currently, anti-VEGF medications like conbercept are frequently used to treat DME, although opinions on their effectiveness in clinical settings vary. Alpha-lipoic acid, a natural antioxidant, can neutralize various reactive oxygen species and free radicals in the body, potentially lowering VEGF levels. Combining alpha-lipoic acid with conbercept may improve treatment outcomes. However, there is a lack of clear experimental studies examining the clinical effectiveness of this combination. Therefore, our project aims to investigate the clinical efficacy of \u0026alpha;-lipoic acid capsules in conjunction with conbercept intravitreal injections for treating patients with diabetic macular edema, with the intention of providing valuable insights for clinical practice. The findings are detailed below.\u003c/p\u003e"},{"header":"1 Data and Methods","content":"\u003cp\u003e1.1 General Information\u0026nbsp; A total of 123 patients (123 eyes) diagnosed with diabetic macular edema who visited our hospital between January 2023 and December 2023 were included in this study. They were divided into three groups based on different treatment regimens: the placebo control group (n=37), the conbercept intravitreal injection group (IVC) (n=42), the conbercept vitreous cavity injection combined with alpha-lipoic acid capsule treatment group (n=44). There were no statistically significant differences in general characteristics among the three groups (P\u0026gt;0.05). This study was approved by the hospital ethics committee, and all patients and their families provided informed consent and signed informed consent forms.\u003c/p\u003e\n\u003cp\u003eInclusion criteria: (1) Clinically diagnosed with type 2 diabetes mellitus with a clear medical history. (2) Diagnosed with macular edema via slit-lamp examination, optical coherence tomography (OCT), fundus fluorescein angiography (FA), or scanning laser ophthalmoscopy (SLO), with central retinal thickness (CRT) in the macular region exceeding 250 \u0026mu;m, and no scarring or proliferative tissue. (3) Unilateral onset. (4) Good mental status, able to cooperate with relevant examinations and treatments; able to tolerate the treatment regimen of this study; signed informed consent form. Exclusion criteria: (1) Macular edema caused by other diseases. (2) Contraindications to the drugs used in this study. (3) Concurrent other retinal diseases such as retinal vein occlusion, age-related macular degeneration, severe glaucoma, and cataracts. (4) Patients who have recently received anti-vascular endothelial growth factor (VEGF) therapy or retinal laser therapy. (5) Patients with refractive media opacity or poor compliance affecting imaging clarity. (6) Patients unable to cooperate with the study.\u003c/p\u003e\n\u003cp\u003e1.2 Treatment Methods (1) Patients in the control group will undergo panretinal photocoagulation (PRP) in multiple sessions over one month. One hour before surgery, compound tropicamide eye drops were used for pupil dilation, and five minutes before surgery, ophthalmic lidocaine hydrochloride eye drops were used for anesthesia. The ZEISS laser ophthalmic treatment instrument was used, and photocoagulation was performed using the Goldmann three-mirror system. The photocoagulation area extended 1 PD above and below the optic disc and 1 PD nasally, and from 1\u0026ndash;2 PD temporally of the macula to the equator. The parameters were set as follows: Energy: 200\u0026ndash;500 mW; laser spot diameter: 200\u0026ndash;300 \u0026mu;m; power: 100\u0026ndash;200 mW; treatment time: 0.2\u0026ndash;0.3 s. (2) Conbercept intravitreal injection (IVC) group: Patients received one IVC (0.5 mg) treatment one week prior to PRP, with PRP initiated one week after injection and completed in multiple sessions within one month. Drug injection was administered using a 3+PRN regimen: one vitreous cavity injection per month (28 days \u0026plusmn; 7 days) for the first three months, followed by injections as needed based on follow-up results after three months. During injection, patients were positioned supine, the affected eye was disinfected, and topical anesthesia was administered. A surgical eye shield was applied, and the eyelids were held open using an eyelid retractor. the conjunctival sac is disinfected with povidone-iodine, and the conjunctival sac is rinsed with 0.9% sodium chloride injection. The sclera is vertically punctured from the ciliary body flat area 4.0 mm from the corneal margin to enter the vitreous cavity, and 0.05 mL of conbercept injection solution (National Drug Approval Number S20130012) is injected，apply pressure to the injection site for 1 minute, apply tobramycin and dexamethasone eye ointment (National Drug Approval Number HJ20181126) to the affected eye postoperatively, and cover with a sterile eye patch. Concurrently, patients are instructed to use antibiotic eye drops for 3\u0026ndash;5 days following injection. (3) In addition to the above, patients in the conbercept vitreous cavity injection combined with \u0026alpha;-lipoic acid capsule treatment group receive oral \u0026alpha;-lipoic acid capsules (Jiangsu Wanhe Pharmaceutical，National Drug Approval Number H20100158) at a dose of 0.2 g per dose, three times daily.\u003c/p\u003e\n\u003cp\u003e1.3 Observation indicators \u0026nbsp;Compare changes in biological indicators such as best-corrected visual acuity (BCVA), central foveal thickness (CFT), microaneurysm (MA) count, superoxide dismutase (SOD) content in aqueous humor, ganglion cell layer (GCL) thickness, hard exudate (HE) area, and hemorrhage area before and after treatment among the three groups. (1) Best-corrected visual acuity (BCVA). The ETDRS visual acuity chart was used to measure visual acuity at baseline, 6 months post-treatment, and 12 months post-treatment. For statistical analysis, BCVA was converted to logarithm of minimum angle of resolution (logMAR). (2) Central foveal thickness (CFT): 6 months post-treatment, and 12 months post-treatment, an optical coherence tomography (Zeiss CIRRUS HD-OCT) was used to scan the retina centered on the macular fovea. The vertical distance from the inner limiting membrane of the retinal neuroepithelium to the inner side of the strongly reflective band of the pigment epithelium was measured as CFT, with three repeated measurements averaged as the final result. (3) Microaneurysm (MA) count: Observed using fundus fluorescein angiography (FA). (４) Superoxide dismutase (SOD) content in aqueous humor: Aqueous humor samples were collected from patients at baseline, 6 months post-treatment, and 12 months post-treatment. SOD expression in the aqueous humor was measured using an enzyme-linked immunosorbent assay (ELISA). (5) Ganglion cell layer (GCL) thickness: Scanning was performed using an optical coherence tomography scanner (Zeiss CIRRUS HD-OCT) at baseline, 6 months post-treatment, and 12 months post-treatment. The vertical distance from the inner plexiform layer to the inner side of the nerve fiber layer in the affected eye was measured as the GCL thickness, with three repeated measurements averaged to obtain the final result. (6) Hard exudate (HE) area: Observed using fundus laser scanning imaging technology (Scanning Laser Ophthalmoscope, SLO). (7) Hemorrhage area: Observed using fundus laser scanning imaging (Scanning Laser Ophthalmoscope, SLO).\u003c/p\u003e\n\u003cp\u003e1.4 Statistical methods \u0026nbsp;The data were analyzed with SPSS 22.0 statistical software. Continuous variables that followed a normal distribution were presented as mean \u0026plusmn; standard deviation. To compare different time points within the same group, repeated measures analysis of variance was utilized. Categorical variables were represented as percentages and assessed using the chi-square test. A P value of less than 0.05 was deemed statistically significant.\u003c/p\u003e"},{"header":"2 Results","content":"\u003cp\u003e2.1 Comparison of general clinical data between the two groups of patients \u0026nbsp;There were no statistically significant differences in general clinical data such as gender, age, duration of diabetes, and smoking history between the three groups of patients (all P \u0026gt; 0.05, Table 1).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 1\u003c/strong\u003e General information of patients\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"561\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 118px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 107px;\"\u003e\n \u003cp\u003eIVC\u0026nbsp;group (n=42)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 107px;\"\u003e\n \u003cp\u003eCombined group (n=44)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 107px;\"\u003e\n \u003cp\u003ethe \u0026nbsp;control\u0026nbsp;group\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; (n=37)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 64px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003et，c2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 58px;\"\u003e\n \u003cp\u003eP\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 118px;\"\u003e\n \u003cp\u003eSex\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 107px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 107px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 107px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 64px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 58px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 118px;\"\u003e\n \u003cp\u003eMale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 107px;\"\u003e\n \u003cp\u003e22（52.4%）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 107px;\"\u003e\n \u003cp\u003e21（47.7%）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 107px;\"\u003e\n \u003cp\u003e18（48.6%）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 64px;\"\u003e\n \u003cp\u003e0.205\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 58px;\"\u003e\n \u003cp\u003e0.9026\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 118px;\"\u003e\n \u003cp\u003eFemale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 107px;\"\u003e\n \u003cp\u003e20（47.6%）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 107px;\"\u003e\n \u003cp\u003e23（52.3%）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 107px;\"\u003e\n \u003cp\u003e19（51.4%）\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 118px;\"\u003e\n \u003cp\u003eAge\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 107px;\"\u003e\n \u003cp\u003e65.95\u0026plusmn;4.06\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 107px;\"\u003e\n \u003cp\u003e64.66\u0026plusmn;4.04\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 107px;\"\u003e\n \u003cp\u003e64.68\u0026plusmn;3.50\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 64px;\"\u003e\n \u003cp\u003e1.501\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 58px;\"\u003e\n \u003cp\u003e0.2273\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 118px;\"\u003e\n \u003cp\u003eOnset time (month)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 107px;\"\u003e\n \u003cp\u003e1.87\u0026plusmn;0.50\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 107px;\"\u003e\n \u003cp\u003e1.90\u0026plusmn;0.45\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 107px;\"\u003e\n \u003cp\u003e1.96\u0026plusmn;0.57\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 64px;\"\u003e\n \u003cp\u003e0.323\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 58px;\"\u003e\n \u003cp\u003e0.7301\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 118px;\"\u003e\n \u003cp\u003eBCVA (logMAR)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 107px;\"\u003e\n \u003cp\u003e0.68\u0026plusmn;0.0.13\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 107px;\"\u003e\n \u003cp\u003e0.71\u0026plusmn;0.12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 107px;\"\u003e\n \u003cp\u003e0.71\u0026plusmn;0.13\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 64px;\"\u003e\n \u003cp\u003e0.840\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 58px;\"\u003e\n \u003cp\u003e0.4350\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 118px;\"\u003e\n \u003cp\u003eCFT （mm）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 107px;\"\u003e\n \u003cp\u003e457.35\u0026plusmn;31.88\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 107px;\"\u003e\n \u003cp\u003e453.92\u0026plusmn;38.63\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 107px;\"\u003e\n \u003cp\u003e445.24\u0026plusmn;32.82\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 64px;\"\u003e\n \u003cp\u003e1.261\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 58px;\"\u003e\n \u003cp\u003e0.2882\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 118px;\"\u003e\n \u003cp\u003eMA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 107px;\"\u003e\n \u003cp\u003e125.46\u0026plusmn;29.96\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 107px;\"\u003e\n \u003cp\u003e121.76\u0026plusmn;32.35\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 107px;\"\u003e\n \u003cp\u003e116.63\u0026plusmn;29.99\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 64px;\"\u003e\n \u003cp\u003e0.812\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 58px;\"\u003e\n \u003cp\u003e0.4478\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 118px;\"\u003e\n \u003cp\u003eDiabetes history (year)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 107px;\"\u003e\n \u003cp\u003e6.14\u0026plusmn;1.26\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 107px;\"\u003e\n \u003cp\u003e6.02\u0026plusmn;1.09\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 107px;\"\u003e\n \u003cp\u003e6.11\u0026plusmn;1.51\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 64px;\"\u003e\n \u003cp\u003e0.101\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 58px;\"\u003e\n \u003cp\u003e0.9075\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 118px;\"\u003e\n \u003cp\u003eSmoking history\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 107px;\"\u003e\n \u003cp\u003e11(26.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 107px;\"\u003e\n \u003cp\u003e10(22.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 107px;\"\u003e\n \u003cp\u003e8（21.6%）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 64px;\"\u003e\n \u003cp\u003e0.255\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 58px;\"\u003e\n \u003cp\u003e0.8801\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 118px;\"\u003e\n \u003cp\u003eNumber of injection\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 107px;\"\u003e\n \u003cp\u003e5.66\u0026plusmn;1.20\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 107px;\"\u003e\n \u003cp\u003e4.45\u0026plusmn;0.90\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 107px;\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 64px;\"\u003e\n \u003cp\u003e5.305\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 58px;\"\u003e\n \u003cp\u003e0.0000\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e2.2 Comparison of BCVA Among the Three Groups of Patients at Different Time Points \u0026nbsp;\u003c/p\u003e\n\u003cp\u003eBefore treatment, there were no statistically significant differences in BCVA among the three groups. At 12 months post-treatment, there were no significant changes in the placebo control group, while the BCVA (log MAR) in the IVC group and the IVC combined with \u0026alpha;-lipoic acid capsule treatment group improved compared to pre-treatment levels, with statistically significant differences (P \u0026lt; 0.05; P \u0026lt; 0.05). At 12 months post-treatment, the differences between the placebo control group and the IVC group, as well as between the placebo control group and the combined treatment group, were statistically significant (P \u0026lt; 0.05; P \u0026lt; 0.05). However, the difference between the conbercept group and the combined treatment group was not statistically significant (P \u0026gt; 0.05). (Table 2)\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 2\u003c/strong\u003e Comparison of BCVA before and after treatment between the two groups of patients\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" align=\"\" width=\"498\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 106px;\"\u003e\n \u003cp\u003ePre－ treatment BCVA（logMA）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 76px;\"\u003e\n \u003cp\u003e６months post-treatment BCVA（logM）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 95px;\"\u003e\n \u003cp\u003e12 months post-treatment BCVA（logMAR）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 55px;\"\u003e\n \u003cp\u003e\u003cem\u003eF\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e\u003cem\u003e \u003c/em\u003e\u003cem\u003eP\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003eIVC\u0026nbsp;group (n=42)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e0.68\u0026plusmn;0.0.13\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 83px;\"\u003e\n \u003cp\u003e0.42\u0026plusmn;0.11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 110px;\"\u003e\n \u003cp\u003e0.42\u0026plusmn;0.12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 55px;\"\u003e\n \u003cp\u003e67.88\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e0.0000\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003eCombined group (n=44)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 83px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.71\u0026plusmn;0.12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 83px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.44\u0026plusmn;0.10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 110px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.40\u0026plusmn;0.12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 55px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e101.26\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 83px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.0000\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003ethe \u0026nbsp;control group (n=37)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 83px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.71\u0026plusmn;0.13\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 83px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.70\u0026plusmn;0.10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 110px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.69\u0026plusmn;0.12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 55px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.48\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 83px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.6191\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e\u003cem\u003eF\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e0.84\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 83px;\"\u003e\n \u003cp\u003e85.82\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 110px;\"\u003e\n \u003cp\u003e68.47\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 55px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e\u003cem\u003eP\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e0.4350\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 83px;\"\u003e\n \u003cp\u003e0.0000\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 110px;\"\u003e\n \u003cp\u003e0.0000\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 55px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e2.3 Comparison of CFT Among the Three Groups of Patients at Different Time Points \u0026nbsp;\u003c/p\u003e\n\u003cp\u003eBefore treatment, there were no statistically significant differences in CFT (\u0026mu;m) among the three groups. At 12 months post-treatment, the control group showed no significant changes, while the CFT (\u0026mu;m) in the IVC group and the IVC combined with \u0026alpha;-lipoic acid capsule treatment group were both reduced compared to pre-treatment levels, with statistically significant differences (P \u0026lt; 0.05; P \u0026lt; 0.05). At 12 months post-treatment, the differences between the blank control group and the IVC group, as well as between the blank control group and the combined group, were statistically significant (P \u0026lt; 0.05; P \u0026lt; 0.05), while the difference between the conbercept group and the combined group was not statistically significant (P \u0026gt; 0.05). (Table 3)\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 3\u003c/strong\u003e Comparison of CFTs before and after treatment between the two groups of patients\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" align=\"\" width=\"498\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003ePre－ treatment\u0026nbsp;CFT（mm）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e６months post-treatment\u0026nbsp;\u0026nbsp;CFT（mm）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e12 months post-treatment\u0026nbsp;CFT（mm）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e\u003cem\u003eF\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e\u003cem\u003eP\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003eIVC\u0026nbsp;group\u0026nbsp;(n=42)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e457.35\u0026plusmn;31.88\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e291.98\u0026plusmn;33.74\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e294.63\u0026plusmn;35.32\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e332.27\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e0.0000\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003eCombined group (n=44)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 83px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e453.92\u0026plusmn;38.63\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 83px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e295.35\u0026plusmn; 33.91\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 83px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e286.65\u0026plusmn;32.99\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 83px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e313.69\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 83px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.0000\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003ethe \u0026nbsp;control group\u003c/p\u003e\n \u003cp\u003e（n=37)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 83px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e445.24\u0026plusmn;32.82\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 83px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e457.22\u0026plusmn;32.38\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 83px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e447.25\u0026plusmn;35.15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 83px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e1.36\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 83px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.2611\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003eF\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e1.26\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e310.11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e268.20\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e\u003cem\u003eP\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e0.2882\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e0.0000\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e0.0000\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e2.4 Comparison of changes in MA counts among the three groups at different time points \u0026nbsp;\u003c/p\u003e\n\u003cp\u003eBefore treatment, there were no statistically significant differences in MA counts among the three groups. At 12 months post-treatment, there were no significant changes in the placebo control group, while MA counts in the IVC group and the IVC combined with \u0026alpha;-lipoic acid capsule treatment group decreased compared to pre-treatment levels, with statistically significant differences (P \u0026lt; 0.05; P \u0026lt; 0.05). At 12 months post-treatment, the differences between the blank control group and the IVC group, as well as between the blank control group and the combined group, were statistically significant (P \u0026lt; 0.05; P \u0026lt; 0.05), while the difference between the conbercept group and the combined group was not statistically significant (P \u0026gt; 0.05). (Table 4)\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 4\u0026nbsp;\u003c/strong\u003eComparison of the number of MA before and after treatment in the two groups of patients\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" align=\"\" width=\"498\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003epre-treatment MA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e６ months post-treatment MA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e12 months post-treatment MA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003eF\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003eP\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003eIVC\u0026nbsp;group (n=42)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e125.46\u0026plusmn;29.96\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e71.59\u0026plusmn;31.37\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e66.75\u0026plusmn;29.83\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e48.28\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e0.0000\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003eCombined group (n=44)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 83px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e121.76\u0026plusmn;32.35\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 83px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e68.58\u0026plusmn;28.88\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 83px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e68.03\u0026plusmn;28.62\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 83px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e46.56\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 83px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.0000\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003ethe \u0026nbsp;control group\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; (n=37)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 83px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e116.63\u0026plusmn;29.99\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 83px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e111.82\u0026plusmn;28.67\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 83px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e115.30\u0026plusmn;28.66\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 83px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.27\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 83px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.7647\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e\u003cem\u003eF\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e0.81\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e25.71\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e35.17\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e\u003cem\u003eP\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e0.4478\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e0.0000\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e0.0000\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e2.5 Comparison of changes in superoxide dismutase (SOD) levels (U/ml) in the aqueous humor of three groups of patients at different time points \u0026nbsp;Before treatment, there were no statistically significant differences in SOD levels in the aqueous humor of the three groups of patients. At 12 months post-treatment, there were no significant changes in SOD levels between the placebo control group and the IVC group, with no statistically significant differences (P \u0026gt; 0.05); however, SOD levels in the IVC combined with \u0026alpha;-lipoic acid capsule treatment group showed a significant increase, with statistically significant differences (P \u0026lt; 0.05). (Table 5)\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 5\u003c/strong\u003e Comparison of superoxide dismutase (SOD) levels (U/ml) before and after treatment between the two groups of patients\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"498\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003epre-treatment SOD（U/ml）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e12 months post-treatment SOD（U/ml）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e12 months post-treatment SOD（U/ml）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003eF\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003eP\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003eIVC\u0026nbsp;group (n=42)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e315.28\u0026plusmn;30.86\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e321.44\u0026plusmn;31.10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e320.56\u0026plusmn;28.77\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e0.51\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e0.6020\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003eCombined group (n=44)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 83px;\"\u003e\n \u003cp\u003e313.67\u0026plusmn;22.11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 83px;\"\u003e\n \u003cp\u003e375.29\u0026plusmn;26.77\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 83px;\"\u003e\n \u003cp\u003e386.52\u0026plusmn;29.38\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 83px;\"\u003e\n \u003cp\u003e98.13\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 83px;\"\u003e\n \u003cp\u003e0.0000\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003ethe \u0026nbsp;control group\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e(n=37)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 83px;\"\u003e\n \u003cp\u003e324.75\u0026plusmn;30.12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 83px;\"\u003e\n \u003cp\u003e317.29\u0026plusmn;28.94\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 83px;\"\u003e\n \u003cp\u003e318.98\u0026plusmn;30.17\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 83px;\"\u003e\n \u003cp\u003e0.64\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 83px;\"\u003e\n \u003cp\u003e0.5294\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003eF\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e1.81\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e52.67\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e72.69\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e\u003cem\u003eP\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e0.1682\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e0.0000\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e0.0000\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e2.6 Comparison of changes in ganglion cell layer thickness (\u0026mu;m) among the three groups of patients at different time points \u0026nbsp;\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eBefore treatment, there were no statistically significant differences in GCL (\u0026mu;m) thickness among the three groups. At 12 months post-treatment, the GCL thickness decreased in the placebo control group, while it increased in the IVC group and the IVC combined with \u0026alpha;-lipoic acid capsule treatment group. However, there were no significant changes in GCL thickness before and after treatment in all three groups, and the differences were not statistically significant (P \u0026gt; 0.05). (Table 6)\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 6\u003c/strong\u003e Comparison of ganglion cell layer thickness ( \u0026mu;m) before and after treatment between the two groups of patients\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"580\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003epre-treatment\u0026nbsp;GCL（mm）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 16px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 93px;\"\u003e\n \u003cp\u003e６\u0026nbsp;months post-treatment\u0026nbsp;GCL（mm）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 95px;\"\u003e\n \u003cp\u003e12 months post-treatment\u0026nbsp;GCL（mm）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 129px;\"\u003e\n \u003cp\u003e\u003cem\u003eF\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e\u003cem\u003eP\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003eIVC\u0026nbsp;group (n=42)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e35.70\u0026plusmn;7.08\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 16px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 93px;\"\u003e\n \u003cp\u003e35.85\u0026plusmn;6.49\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 141px;\"\u003e\n \u003cp\u003e 36.28\u0026plusmn;7.37\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e0.08\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e0.9252\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003eCombined group (n=44)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 83px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e37.12\u0026plusmn;5.19\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 16px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 93px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e37.89\u0026plusmn;6.46\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 141px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003cp\u003e39.55\u0026plusmn;6.60\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 83px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e1.81\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 83px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.1674\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003ethe \u0026nbsp;control group\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e(n=37)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 83px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e36.17\u0026plusmn;6.40\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 16px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 93px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e36.44\u0026plusmn;5.56\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 141px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e 5.17\u0026plusmn;5.39\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 83px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.49\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 83px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.6138\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e\u003cem\u003eF\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e0.58\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 16px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 93px;\"\u003e\n \u003cp\u003e1.23\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 141px;\"\u003e\n \u003cp\u003e5.01\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e\u003cem\u003eP\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e0.5615\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 16px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 93px;\"\u003e\n \u003cp\u003e0.2950\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 141px;\"\u003e\n \u003cp\u003e0.0081\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 83px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 93px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 95px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 46px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e2.7 Comparison of changes in the area of hard exudate (mm\u0026sup2;) among the three groups of patients at different time points \u0026nbsp;\u003c/p\u003e\n\u003cp\u003eBefore treatment, there were no statistically significant differences in the area of hard exudate (mm\u0026sup2;) among the three groups. At 12 months post-treatment, the area of hard exudate improved in all three groups compared to pre-treatment levels. Among these, the IVC group and the IVC combined with \u0026alpha;-lipoic acid capsule treatment group showed statistically significant differences compared to pre-treatment levels (P \u0026lt; 0.05). (Table 7)\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable7\u003c/strong\u003e Comparison of hard exudate area (mm2) before and after treatment between the\u0026nbsp;two groups of patients\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 81px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 111px;\"\u003e\n \u003cp\u003eHE\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 93px;\"\u003e\n \u003cp\u003epre-treatment\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 119px;\"\u003e\n \u003cp\u003e12 months post-treatment\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e\u003cem\u003e\u0026chi;\u003c/em\u003e\u003cem\u003e\u003csup\u003e2\u003c/sup\u003e\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 81px;\"\u003e\n \u003cp\u003e\u003cem\u003eP\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"3\" style=\"width: 81px;\"\u003e\n \u003cp\u003eIVC group (n=42)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 111px;\"\u003e\n \u003cp\u003e\u0026lt;1.5mm\u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 93px;\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 119px;\"\u003e\n \u003cp\u003e15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"3\" style=\"width: 83px;\"\u003e\n \u003cp\u003e14.365\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"3\" style=\"width: 81px;\"\u003e\n \u003cp\u003e0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 111px;\"\u003e\n \u003cp\u003e1.5mm\u003csup\u003e2\u003c/sup\u003e-3.5mm\u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 93px;\"\u003e\n \u003cp\u003e35\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 119px;\"\u003e\n \u003cp\u003e20\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 111px;\"\u003e\n \u003cp\u003e\u0026gt;3.5mm\u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 93px;\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 119px;\"\u003e\n \u003cp\u003e7\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"3\" style=\"width: 81px;\"\u003e\n \u003cp\u003eCombined group (n=44)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 111px;\"\u003e\n \u003cp\u003e\u0026lt;1.5mm\u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 93px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 119px;\"\u003e\n \u003cp\u003e12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"3\" style=\"width: 83px;\"\u003e\n \u003cp\u003e35.969\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"3\" style=\"width: 81px;\"\u003e\n \u003cp\u003e0.000\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 111px;\"\u003e\n \u003cp\u003e1.5mm\u003csup\u003e2\u003c/sup\u003e-3.5mm\u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 93px;\"\u003e\n \u003cp\u003e36\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 119px;\"\u003e\n \u003cp\u003e28\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 111px;\"\u003e\n \u003cp\u003e\u0026gt;3.5mm\u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 93px;\"\u003e\n \u003cp\u003e7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 119px;\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"3\" style=\"width: 81px;\"\u003e\n \u003cp\u003ethe \u0026nbsp;control group (n=37)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 111px;\"\u003e\n \u003cp\u003e\u0026lt;1.5mm\u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 93px;\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 119px;\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"3\" style=\"width: 83px;\"\u003e\n \u003cp\u003e3.648\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"3\" style=\"width: 81px;\"\u003e\n \u003cp\u003e0.162\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 111px;\"\u003e\n \u003cp\u003e1.5mm\u003csup\u003e2\u003c/sup\u003e-3.5mm\u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 93px;\"\u003e\n \u003cp\u003e25\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 119px;\"\u003e\n \u003cp\u003e31\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 111px;\"\u003e\n \u003cp\u003e\u0026gt;3.5mm\u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 93px;\"\u003e\n \u003cp\u003e9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 119px;\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 81px;\"\u003e\n \u003cp\u003e\u003cem\u003e\u0026chi;\u003c/em\u003e\u003cem\u003e\u003csup\u003e2\u003c/sup\u003e\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 111px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 93px;\"\u003e\n \u003cp\u003e3.988\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 119px;\"\u003e\n \u003cp\u003e11.971\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 164px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 81px;\"\u003e\n \u003cp\u003e\u003cem\u003eP\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 111px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 93px;\"\u003e\n \u003cp\u003e0.408\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 119px;\"\u003e\n \u003cp\u003e0.018\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 164px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e2.8 Comparison of changes in bleeding area (mm\u0026sup2;) among the three groups of patients at different time points \u0026nbsp;\u003c/p\u003e\n\u003cp\u003eBefore treatment, there were no statistically significant differences in bleeding area (mm\u0026sup2;) among the three groups. At 12 months post-treatment, bleeding area improved in all three groups compared to pre-treatment levels, with statistically significant differences (P \u0026lt; 0.05). (Table 8)\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 8\u003c/strong\u003e Comparison of haemorrhage area (mm2) before and after treatment between the two groups of patients\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 67px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003ehaemorrhage area (mm2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003epre-treatment\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 88px;\"\u003e\n \u003cp\u003e12 months post-treatment\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 58px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 71px;\"\u003e\n \u003cp\u003e\u003cem\u003e\u0026chi;\u003c/em\u003e\u003cem\u003e\u003csup\u003e2\u003c/sup\u003e\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 48px;\"\u003e\n \u003cp\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 66px;\"\u003e\n \u003cp\u003e\u003cem\u003eP\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"3\" style=\"width: 67px;\"\u003e\n \u003cp\u003eIVC\u0026nbsp;group (n=42)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e\u0026lt;2mm\u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 88px;\"\u003e\n \u003cp\u003e36\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 58px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" rowspan=\"3\" style=\"width: 71px;\"\u003e\n \u003cp\u003e55.5877\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 48px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"3\" style=\"width: 66px;\"\u003e\n \u003cp\u003e0.0000\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e2mm\u003csup\u003e2\u003c/sup\u003e-4mm\u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003e35\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 88px;\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 58px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 48px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e\u0026gt;4mm\u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 88px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 58px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 48px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"3\" style=\"width: 67px;\"\u003e\n \u003cp\u003eCombined group (n=44)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e\u0026lt;2mm\u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 88px;\"\u003e\n \u003cp\u003e39\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 58px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" rowspan=\"3\" style=\"width: 71px;\"\u003e\n \u003cp\u003e55.8386\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 48px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"3\" style=\"width: 66px;\"\u003e\n \u003cp\u003e0.0000\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e2mm\u003csup\u003e2\u003c/sup\u003e-4mm\u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003e27\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 88px;\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 58px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 48px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e\u0026gt;4mm\u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003e13\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 88px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 58px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 48px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"3\" style=\"width: 67px;\"\u003e\n \u003cp\u003ethe \u0026nbsp;control group (n=\u003c/p\u003e\n \u003cp\u003e37)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e\u0026lt;2mm\u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 88px;\"\u003e\n \u003cp\u003e23\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 58px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" rowspan=\"3\" style=\"width: 71px;\"\u003e\n \u003cp\u003e27.9844\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 48px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"3\" style=\"width: 66px;\"\u003e\n \u003cp\u003e0.0000\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e2mm\u003csup\u003e2\u003c/sup\u003e-4mm\u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003e27\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 88px;\"\u003e\n \u003cp\u003e13\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 58px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 48px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e\u0026gt;4mm\u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003e8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 88px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 58px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 48px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 67px;\"\u003e\n \u003cp\u003e\u0026chi;2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003e5.3229\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 88px;\"\u003e\n \u003cp\u003e10.9740\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 58px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" style=\"width: 116px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 67px;\"\u003e\n \u003cp\u003e\u003cem\u003eP\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003e0.2557\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 88px;\"\u003e\n \u003cp\u003e0.0269\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 58px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" style=\"width: 116px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 74px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 92px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 71px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 71px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 59px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 1px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 53px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e"},{"header":"3 Discussion","content":"\u003cp\u003eDM is characterized by an increase in central macular thickness (CMT). In the early stages of the disease, patients may experience symptoms such as blurred vision and visual distortions, which can impair normal daily activities. If not addressed in the advanced stages, there is a significant risk of blindness.\u003c/p\u003e\n\u003cp\u003eThese symptoms are closely related to the destructive effects of hyperglycemia on blood vessels, leading to retinal ischemia and hypoxia, which in turn results in increased release of VEGF. VEGF is a disulfide-linked dimeric glycoprotein, belonging to the class of peptide growth factors. It was first isolated and purified from the culture medium of bovine pituitary follicular stellate cells by Ferrara et al. in 1989\u003csup\u003e６\u003c/sup\u003e.Among the VEGF family, VEGF-A is most abundantly expressed in the ocular vascular system and neovascular tissues, and many ocular vascular proliferative diseases are closely associated with its regulation and expression.⁷ Additionally, hyperglycemia also causes oxidative stress in the body. In patients with diabetic retinopathy (DR), there is an elevation in the levels of oxygen free radicals, lipid peroxides, and malondialdehyde (MDA), whereas the activity of antioxidant defense enzymes that help eliminate free radicals, including superoxide dismutase (SOD), glutathione reductase, glutathione peroxidase, and catalase, is diminished⁸. Typically, the body\u0026apos;s oxidative and antioxidant systems maintain a balance. However, when the production of free radicals surpasses the ability of the antioxidant defense system to eliminate them, it leads to a disruption in redox homeostasis. The retina is particularly vulnerable to oxidative stress damage because of its high metabolic activity.Reactive oxygen species (ROS) amplify inflammatory responses by activating the protein kinase C (PKC) pathway or triggering the activation of the central inflammatory mediator nuclear factor-\u0026kappa;B (NF-\u0026kappa;B), thereby upregulating the expression of vascular endothelial growth factor (VEGF) protein.\u003c/p\u003e\n\u003cp\u003eThe current standard treatment for DME involves intravitreal injections of anti-VEGF drugs.\u0026sup1;\u0026sup1; Conbercept is a domestically produced anti-VEGF drug in China that binds to IgG-Fc fusion proteins in the body to block VEGF signaling. However, such drugs have a short half-life, limited duration of action, and poor specificity.\u0026sup1;\u0026sup2;⁻\u0026sup1;\u0026sup3; Frequent intravitreal injections also increase the incidence of endophthalmitis, posing certain safety risks for clinical use. Additionally, the high cost of these drugs results in poor compliance among some patients. Alpha-lipoic acid is a natural antioxidant that helps remove different reactive oxygen species and free radicals from the body. It also binds to metal ions to inhibit the formation of free radicals, enhances the function of endothelial nitric oxide synthase (eNOS), and works together with other antioxidants like glutathione (GSH), vitamin C, and vitamin E to produce combined antioxidant benefits.The antioxidant action of \u0026alpha;-lipoic acid is mediated through the stabilization and nuclear translocation of the nuclear factor erythroid 2-related factor 2 (Nrf2)\u0026sup1;⁶, which controls the expression of key genes involved in ROS elimination through the Nrf2 antioxidant response element signaling pathway, such as those encoding SOD and the catalytic subunit of glutathione S-transferase\u003csup\u003e17\u003c/sup\u003e. Nrf2 can also block NF-\u0026kappa;B activation, thereby alleviating oxidative stress. Zhang Xinfang et al. found that \u0026alpha;-lipoic acid capsules can reduce vascular endothelial damage, inhibit neovascularization, and alleviate symptoms and effectively controlling the condition\u003csup\u003e１８\u003c/sup\u003e. In addition to its effects on oxidative stress within the body, \u0026alpha;-LA is also believed to play a role in blood glucose control. In a study conducted by Yoon Sook Kim and colleagues, it was observed that in mouse models of diabetes induced by STZ, the control group experienced a notable rise in blood glucose levels, whereas the mice that received \u0026alpha;-LA treatment kept their blood glucose levels within the normal range for the duration of the experiment\u003csup\u003e１９\u003c/sup\u003e.\u003c/p\u003e\n\u003cp\u003eThis study investigated the efficacy of \u0026alpha;-lipoic acid capsules combined with conbercept intravitreal injection for the treatment of diabetic macular edema, and compared the results with those of patients who received conbercept intravitreal injection alone. The results showed that the best-corrected visual acuity (BCVA), central foveal thickness (CFT), and number of microaneurysms (MA) improved in all three groups over time. Patients with macular edema have a large number of neovascularization, which, due to their fragility and thin vessel walls, lead to the formation of microaneurysms. Additionally, the high permeability of neovascularization causes excessive fluid leakage and accumulation between retinal layers, resulting in increased CFT. BCVA is a critical functional outcome metric for assessing treatment efficacy. Previously, Li Shuang and colleagues discovered that administering three consecutive intravitreal injections of conbercept for diabetic macular edema (DME) led to a significant decrease in central foveal thickness (CFT), reduced macular edema, and enhanced visual acuity, indicating both effectiveness and safety. The results of this study also showed that after 12 months of treatment, there were no significant changes in the control group, while the BCVA (log MAR) in the conbercept group and the conbercept combined with \u0026alpha;-lipoic acid capsule treatment group improved from (0.68 \u0026plusmn; 0.13) and (0.71 \u0026plusmn; 0.12) to (0.42 \u0026plusmn; 0.12) and (0.40 \u0026plusmn; 0.12), respectively, with the combined group showing better BCVA than the conbercept treatment group, suggesting that \u0026alpha;-lipoic acid can better promote visual recovery in DME patients. The CFT (\u0026mu;m) in both groups decreased from (457.35 \u0026plusmn; 31.88) (453.92 \u0026plusmn; 38.63) to (294.63 \u0026plusmn; 35.32) and (286.65 \u0026plusmn; 32.99), respectively, indicating that both conbercept and \u0026alpha;-lipoic acid can reduce VEGF, regulate the permeability of the blood-retinal barrier, and alleviate macular edema.\u003c/p\u003e\n\u003cp\u003eThis study found that only the group treated with a combination of conbercept and \u0026alpha;-lipoic acid capsules showed significant changes in superoxide dismutase (SOD) levels in the aqueous humor, which increased from 313.67 \u0026plusmn; 22.11 to 386.52 \u0026plusmn; 29.38 U/ml, with a statistically significant difference (P \u0026lt; 0.05). This indicates that, compared to treatment with conbercept alone, \u0026alpha;-lipoic acid can reduce oxidative stress-induced damage to the retina by enhancing the expression of SOD.Common indicators of free radical levels in the body include malondialdehyde (MDA) and SOD. MDA reflects oxidative stress levels, while SOD indicates antioxidant defense capacity. In a study by Yu Wenfeng et al., diabetic patients without retinopathy exhibited significantly elevated MDA levels and significantly reduced SOD levels compared to healthy controls. This indicates that individuals with diabetes, even without diabetic retinopathy (DR), experience a significant level of oxidative stress\u003csup\u003e２１\u003c/sup\u003e.In an animal experiment conducted by Zhou Jin et al., the group treated with \u0026alpha;-lipoic acid showed decreased MDA levels and increased SOD levels compared to the non-treated diabetic group. Many other studies have also shown that reactive oxygen species (ROS) production increases in bovine retinal endothelial cells or human retinal endothelial cells exposed to high glucose levels\u003csup\u003e２２\u003c/sup\u003e. Incorporating cytoplasmic copper/zinc-dependent SOD into the culture medium can help avert cell death caused by elevated glucose levels. These findings are consistent with the outcomes of this study. Superoxide is the primary reactive species responsible for oxidative stress in diabetes. Research by Kanwar et al. indicated that diabetic mice generated more superoxide in their retinas than normal control mice\u003csup\u003e２３\u003c/sup\u003e. During the secretion of retinal vascular endothelial growth factor (VEGF), the oxidant nitrotyrosine and the nuclear transcription factor NF-kB are crucial players. \u0026alpha;-Lipoic acid can reduce the expression of retinal VEGF and limit the formation of new blood vessels by inhibiting the activation of these two oxidants and curbing the excessive production of superoxide radicals.\u003csup\u003e２４\u003c/sup\u003e.\u003c/p\u003e\n\u003cp\u003eIn terms of changes in the area of hard exudates (mm\u0026sup2;), all three groups showed improvement compared to pre-treatment levels. Hard exudates (HE) in the retina appear as yellowish-white deposits found in the outer plexiform layer, primarily composed of lipids and proteins, indicating damage to capillary endothelial cells. If they occur in the fovea centralis, they can cause significant vision impairment. Studies have shown that treatment with conbercept for PDR resulted in a significant reduction in HE area at each follow-up time point compared to the initial month\u003csup\u003e 25\u0026ndash;26\u003c/sup\u003e\u003csup\u003e．\u003c/sup\u003e, similar to the results of this study. The results of this study show that in the combination therapy group, the area of exudates greater than 3.5 mm\u0026sup2;, those in the 1.5 mm\u0026sup2;\u0026ndash;3.5 mm\u0026sup2; range decreased, and those less than 1.5 mm\u0026sup2; increased, with the most significant changes observed. We speculate that compared to monotherapy with laser or conbercept, \u0026alpha;-lipoic acid may have a superior protective effect on retinal capillary endothelial cells.\u003c/p\u003e\n\u003cp\u003eFurther analysis of changes in hemorrhage area (mm\u0026sup2;) before and after treatment revealed that hemorrhage area improved in all three groups compared to pre-treatment levels.Conbercept significantly reduces VEGF levels by inhibiting its binding to receptors, while \u0026alpha;-lipoic acid blocks excessive superoxide formation and inhibits retinal VEGF expression. Both agents inhibit retinal neovascularization and reduce retinal hemorrhage.\u003c/p\u003e\n\u003cp\u003eIn terms of changes in ganglion cell layer thickness (\u0026mu;m), domestic studies have used automated full-threshold microperimetry to measure ganglion cell layer thickness and microperimetry changes, finding that a reduction in ganglion cell layer (GCL) thickness is associated with improvements in best-corrected visual acuity (BCVA) and has the best predictive effect on BCVA improvements. This indicates that once macular edema subsides, enhancements in vision, microfield improvements, and neuronal recovery are linked to a decrease in GCL thickness\u003csup\u003e２７\u003c/sup\u003e. Retinal ganglion cells serve as an ideal model for studying new treatment methods for retinal degenerative diseases (particularly diabetic retinopathy), and alpha-lipoic acid can protect ganglion cells and reduce apoptosis\u003csup\u003e２８\u003c/sup\u003e. Animal studies have reported reduced retinal ganglion cell counts in diabetic animals, and the number of RGCs in the retinas of mice treated with alpha-lipoic acid was significantly increased compared to diabetic mice. Alpha-lipoic acid can restore the normal activity of the Na+/K+-ATPase enzyme in the neuronal cell membranes of diabetic rats, increase the production of inositol in the neuronal membranes, and improve neuronal damage\u003csup\u003e２９\u003c/sup\u003e. However, the results of this study showed that after 12 months of treatment, the GCL (\u0026mu;m) in the control group, the conbercept group, and the combined group changed from (36.17 \u0026plusmn; 6.40), (35.70 \u0026plusmn; 7.08), and (37.12 \u0026plusmn; 5.19) to (35.17 \u0026plusmn; 5.39), (36.28 \u0026plusmn; 7.37), and (39.55 \u0026plusmn; 6.60), respectively, with no significant improvement before and after treatment (P \u0026gt; 0.05). We believe that the brief follow-up period could be a reason for not detecting notable changes in the indicators. Additional long-term studies are necessary to better understand the impact of anti-VEGF therapy and \u0026alpha;-lipoic acid therapy on the thickness of the retinal ganglion cell layer and the quantity of ganglion cells.\u003c/p\u003e\n\u003cp\u003eIn terms of injection frequency, the average number of injections in the conbercept group was 5.66 \u0026plusmn; 1.20, which was higher than the 4.45 \u0026plusmn; 0.90 in the combination group. This suggests that conbercept treatment for DME may increase the number of injections and patient discomfort, while the combination therapy with alpha-lipoic acid may have advantages in fewer injections, reduced costs, and lower risks related to the injections.\u003c/p\u003e\n\u003cp\u003eRetinal laser photocoagulation therapy also has a certain therapeutic effect on DME patients, but this method can damage ocular tissues and induce complications such as blurred vision and vitreous hemorrhage. Not every DME patient who receives laser therapy sees a decrease in edema, indicating that laser therapy has its constraints\u0026sup3;⁰⁻\u0026sup3;\u0026sup1;．Based on this, we applied anti-VEGF and \u0026alpha;-lipoic acid therapy to patients and compared the efficacy of the two treatment regimens. In summary, at 12 months post-treatment, \u0026alpha;-lipoic acid therapy demonstrated significantly superior outcomes compared to conbercept therapy in terms of best-corrected visual acuity (BCVA), hard exudate (HE) area, hemorrhage area, changes in superoxide dismutase (SOD) levels in aqueous humor, and number of injections. However, this study had a small sample size and a short observation period, which is insufficient to conclusively demonstrate the long-term differences in treatment efficacy. Further research involving larger participant groups and extended follow-up times is necessary to determine the long-term effectiveness of \u0026alpha;-lipoic acid treatment for diabetic macular edema. This will help in its clinical use to enhance and sustain the visual outcomes for patients with DME over time.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003e\u003cem\u003eAcknowledgements\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study is the culmination of a long and arduous journey. I have only been able to make it due to the dedicated support from Qilu Hospital, Shandong University.My deepest and sincerest gratitude goes to my supervisor Shuting Li , for her continuous and invaluable guidance throughout my research.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eFunding\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNo funding or sponsorship was received for this study or publication of this article.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eAuthor Contributions\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;Conceptualisation: Shuting Li. Formal analysis:\u0026nbsp;Aolin Han.\u0026nbsp;Writing-original draft preparation and editing: Jie Wang. Methodology:\u0026nbsp; Yuanqing Liu，Lingchao Zhang. Validation: Hong Wang, Pengfei Jiang.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eDisclosures\u0026nbsp;\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no conflict of interest.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eCompliance with Ethics Guidelines\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe study was approved by the Ethical Committee of Qilu Hospital of Shandong University (approval no. 2021051).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eData Availability\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eThanking Patient Participant(s)\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThanks for the contributions of all patients and volunteers.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003ePrior Presentation\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eLi Binbin, Tan Meihua, Yin Zhangliang. Comparison of the efficacy of different dosing regimens of Conbercept in the treatment of clinically significant diabetic macular edema. International Journal of Ophthalmology. 2022;22(1):130-134\u003c/li\u003e\n\u003cli\u003eZhang Hanwen, Shi Yan. Advances in Research on the Mechanisms of Diabetic Retinopathy and Blood-Retinal Barrier Damage. Chinese Journal of Retinal Diseases. 2013;29(6):6113-6137\u003c/li\u003e\n\u003cli\u003eWan Guangming, Xue Rong. Discussion on the pathogenesis and prevention and treatment strategies of diabetic retinopathy from the perspective of retinal oxidative stress and microvascular changes [J]. Advances in Ophthalmology, 2022, 42(7):505-509\u003c/li\u003e\n\u003cli\u003eGuo Mi, Bian Hongxia, Bian Mengting, Yao Yanyan, Ma Guomin. Effect of Conbercept Treatment on the Retinal Ellipsoid Zone in Different OCT Subtypes of Diabetic Macular Edema. Journal of Clinical Ophthalmology. 2023, 31(2):121\u0026ndash;125.\u003c/li\u003e\n\u003cli\u003eChristine Altmann and Mirko H，H. Schmidt. The Role of Microglia in Diabetic Retinopathy: Inflammation, Microvasculature Defects and Neurodegeneration.Molecular Sciences.2018;19(110):1-31\u003c/li\u003e\n\u003cli\u003eXu Shanshan, Zhang Chong. Application and Research Progress of Anti-Vascular Endothelial Growth Factor Drugs in the Treatment of Ophthalmic Diseases. Journal of Clinical Drug Therapy. 2020;18(2):6-11\u003c/li\u003e\n\u003cli\u003eXu Juan, Gao Yun, Yue Feng. Effects of \u0026alpha;-Lipoic Acid on Vascular Endothelial Growth Factor in Patients with Diabetic Retinopathy. Journal of Taishan Medical College. 2012;33(4):250-251\u003c/li\u003e\n\u003cli\u003eSul Gee Lee, Chang Gun Lee，Il Han Yun.Effect of lipoic acid on expression of angiogenic factors in diabetic rat retina. Clinical \u0026amp; Experimental Ophthalmology. 2011;40(1):47-57\u003c/li\u003e\n\u003cli\u003eCameron D. Haydinger. Genevieve F. Oliver. Liam M. Ashander. Justine R. Smith.Oxidative Stress and Its Regulation in Diabetic Retinopathy. Antioxidants. 2023；12(8):1-25\u003c/li\u003e\n\u003cli\u003eDi Sha, Wang Tianchu, Pang Bing, Li Min. Research Progress on the Pathogenesis and Treatment of Diabetic Retinopathy. Medical Review. 2021;27 (21):4285-4291\u003c/li\u003e\n\u003cli\u003eXiaolei Sun, Jingjing Zhang, Jingyi Tian, Shijiu Chen, Fanxing Zeng. Comparison of the Efficacy and Safety of Intravitreal Conbercept with Intravitreal Ranibizumab for Treatment of Diabetic Macular Edema: A Meta-Analysis. Journal of Ophthalmology. 2020; 2020:1-8\u003c/li\u003e\n\u003cli\u003eWang Zongqing, Liu Xiangling, Zhou Lixiao, Dong Hongtao, Han Xiaodong. Effects of Laser Combined with Alpha-Lipoic Acid on Central Retinal Artery Hemodynamics and Vascular Endothelial Growth Factor in Diabetic Retinopathy. Clinical Medical Engineering. 2019; 26(12):1637-1638\u003c/li\u003e\n\u003cli\u003eZhao Yang, Shi Yan. 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Ahmet Ayar．Effects of alpha-lipoic acid on retinal ganglion cells, retinal thicknesses, and VEGF production in an experimental model of diabetes．International Ophthalmology．2016；6（３７）：1269-1278．\u003c/li\u003e\n\u003cli\u003eLi Wentao, Wang Rui Feng, Tang Wenjian, Gao Xuexia. The effect of combination therapy with Conbercept and laser photocoagulation on patients with diabetic macular edema. Practical Clinical Medicine Combining Chinese and Western Medicine. 2025;25(1):26-29.\u003c/li\u003e\n\u003cli\u003eWeizhe Meng，Ronghua Li，Xiufen Xie.Conbercept and Retinal Photocoagulation in the treatment of Diabetic Macular Edema. Pakistan Journal of Medical Sciences. 2019;35(6):1493-1498.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-ophthalmology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"boph","sideBox":"Learn more about [BMC Ophthalmology](http://bmcophthalmol.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/boph","title":"BMC Ophthalmology","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"α-lipoic acid capsules, diabetic macular edema, conbercept, endothelial growth factor, neovascularization","lastPublishedDoi":"10.21203/rs.3.rs-7047976/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7047976/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eObjective To investigate the safety and efficacy of α-lipoic acid capsules combined with conbercept intravitreal injection in the treatment of diabetic macular edema.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eMethods A total of 123 patients with 123 eyes diagnosed with diabetic macular edema who visited our hospital from January 2023 to December 2023 were included in this study. Patients were divided into three groups based on treatment regimens: a placebo control group (n=37), a conbercept intravitreal injection group (IVC) (n=42), and a conbercept intravitreal injection combined with α-lipoic acid capsule treatment group (n=44). All patients in each group were followed up for 12 months, and changes in biological indicators such as best-corrected visual acuity (BCVA), central foveal thickness (CFT), microaneurysm (MA) count, superoxide dismutase (SOD) content in aqueous humor, ganglion cell layer (GCL) thickness, hard exudate (HE) area, and hemorrhage area were compared before and after treatment.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eResults In the IVC group and the combination therapy group, BCVA, CFT, and MA count showed significant improvements at 6 and 12 months post-treatment compared to pre-treatment levels (P \u0026lt; 0.05). while the control group showed no significant changes before and after treatment (P \u0026gt; 0.05). The levels of superoxide dismutase (SOD) in the combined treatment group significantly increased at 6 and 12 months post-treatment compared to pre-treatment levels (P \u0026lt; 0.05), while the IVC group and the placebo control group showed no significant changes compared to pre-treatment levels (P \u0026gt; 0.05); the thickness of the ganglion cell layer in all three groups showed no significant improvement at 6 months and 12 months post-treatment compared to pre-treatment levels (P \u0026gt; 0.05); the area of hard exudates in all three groups improved at 6 months and 12 months post-treatment compared to pre-treatment levels, with statistically significant differences observed in the IVC group and combined therapy group compared to pre-treatment levels (P \u0026lt; 0.05); the hemorrhage area in all three groups improved at 6 and 12 months post-treatment compared to pre-treatment levels, with statistically significant differences observed (P \u0026lt; 0.05).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eConclusion In addition to significantly improving visual acuity, reducing foveal thickness, decreasing the number of microaneurysms, and reducing hemorrhagic and hard exudative areas, the addition of α-lipoic acid capsules to conbercept therapy in patients with DME enhances overall efficacy and increases SOD levels in the aqueous humor, making it worthy of clinical application.\u003c/p\u003e","manuscriptTitle":"observation on the efficacy of α-lipoic acid capsules combined with conbercept intravitreal injection in the treatment of diabetic macular edema","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-08-25 06:32:40","doi":"10.21203/rs.3.rs-7047976/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"reviewerAgreed","content":"227660626461303610063181617400691000490","date":"2025-08-16T14:00:49+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-08-16T13:49:43+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2025-08-05T09:30:38+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-07-09T12:38:34+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-07-09T12:38:18+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Ophthalmology","date":"2025-07-04T14:59:42+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-ophthalmology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"boph","sideBox":"Learn more about [BMC Ophthalmology](http://bmcophthalmol.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/boph","title":"BMC Ophthalmology","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"b25f9932-b0b5-4438-8c62-aadfc5621225","owner":[],"postedDate":"August 25th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2025-08-25T06:32:40+00:00","versionOfRecord":[],"versionCreatedAt":"2025-08-25 06:32:40","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-7047976","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7047976","identity":"rs-7047976","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}