目的：评估外用白介素(Interleukin, IL)-6特异性抑制剂托珠单抗滴眼液在调控角膜碱烧伤后修复的安全性和有效性。方法：6只角膜假烧伤小鼠局部使用托珠单抗滴眼(2.5 mg/mL)和6只角膜假烧伤小鼠局部使用生理盐水滴眼，分别作为实验组和空白组以评估托珠单抗滴眼液的安全性。30只碱烧伤小鼠，按照1∶1随机分配到治疗组和对照组，治疗组使用托珠单抗滴眼液滴眼，对照组使用生理盐水，每日6次，连续用14 d。通过前段光学相干断层扫描观察虹膜前粘连、角膜后弹力层脱离及角膜水肿，在体视显微镜下检查角膜瘢痕形成及上皮伤口愈合。在角膜切片上评估IL-6定位、肌成纤维细胞、免疫细胞浸润和角膜上皮化生。在角膜铺片上评估角膜新生血管和新生淋巴管面积。通过实时荧光定量聚合酶链式反应(quantitative real-time polymerase chain reaction, qRT-PCR)方法检测小鼠角膜 IL-6的表达水平。结果：对未进行碱烧伤的角膜使用托珠单抗治疗未观察到明显的角膜结构的损伤。角膜碱烧伤后可见角膜结构的破坏，角膜瘢痕形成并伴有角膜上皮伤口的延迟愈合。使用托珠单抗治疗后，虹膜前粘连的发生率从86.67%下降至20%(P <0.01)，角膜后弹力层脱离的发生率从93.33%下降至53.33%(P <0.05)，角膜厚度小于对照组[(100.03±15.73)μ m vs. (207.02±56.30)μ m，P＜0.001]，角膜混浊评分从对照组的3.76±0.44下降到治疗组的1.94±0.83(P <0.001)，治疗组在第5天(P <0.05)、第10天(P <0.001)和第14天(P <0.001)的上皮愈合率高于对照组。角膜碱烧伤后可见IL-6大量分布于角膜全层，且可见大量肌成纤维细胞形成及免疫细胞浸润，托珠单抗治疗后抑制了IL-6的表达(下降77.5%，P <0.05)，肌成纤维细胞数量从每视野(91.44±65.60)个减少至(12.89±10.51)个(P <0.01)，免疫细胞的数量从每视野(60.30±28.71)个细胞减少至每视野(6.80±3.82)个细胞(P <0.001)。此外，托珠单抗还减少角膜切片中每视野的杯状细胞数目由(11.3±5.29)个减少至(2.0±1.90个)(P <0.01)，并减少角膜新生血管和新生淋巴管的形成(分别减少了76.86%和71.16%，均P <0.001)。结论：局部使用托珠单抗抑制IL-6未见明显角膜毒性，且可以调控角膜碱烧伤后的修复。
Objective: To evaluate the safety and effect of topical IL-6 inhibitor tocilizumab eye drops in regulating corneal alkali burn repair. Methods: Six mice without corneal burns were locally treated with tocilizumab eye drops (2.5 mg/mL) and six mice with corneal pseudo burn were treated with saline, respectively, as experimental and blank groups to evaluate the safety of tocilizumab eye drops. 30 alkali burned mice were randomly divided into a treatment group and a control group in a 1:1 ratio. The treatment group received tocilizumab eye drops, while the control group received physiological saline solution 6 times per day for 14 days. Observe the anterior adhesion of the iris, detachment of the Descemet membrane, and corneal edema through anterior segment optical coherence tomography (AS-OCT), and examine corneal scarring and epithelial wound healing under a stereomicroscope. Evaluate IL-6 localization, myofibroblasts, immune cell infiltration, and corneal epithelial metaplasia on corneal sections. Evaluate corneal neovascularization and neovascularization area by whole-mount cornea staining. Detect the expression level of IL-6 in mouse cornea by qRT-PCR. Results: No significant damage to the corneal structure was observed in the treatment of unburned corneas with tocilizumab. After corneal alkali burns, the corneal structure was damaged, corneal scarring was formed, and delayed healing of corneal epithelial wounds was observed.After treatment with tocilizumab, the incidence of anterior synechia of the iris significantly decreased from 86.67% to 20% (P <0.01), the incidence of Descemet membrane detachment decreased from 93.33% to 53.33% (P <0.05), the corneal thickness was significantly less than that of the control group (100.03±15.73) μ m vs. (207.02±56.30)μ m (P <0.001), the corneal opacity score decreased from 3.76±0.44 in the control group to 1.94±0.83 in the treatment group (P <0.001), and the epithelial healing rate in the treatment group was significantly higher than that in the control group on day 5 (P <0.05), day 10 (P <0.001), and day 14 (P <0.001).After corneal alkali burns, IL-6 was distributed throughout the corneal layer, and a large number of myofibroblasts and immune cells were observed. After treatment with tocilizumab, the expression of IL-6 was inhibited (decreased by 77.5%, P <0.05), the number of myofibroblasts decreased from (91.44±65.60) per field to (12.89±10.51) per field (P <0.01), and the number of immune cells decreased from (60.30±28.71) cells per field to (6.80±3.82) cells per field (P <0.001). In addition, tocilizumab also reduced the number of goblet cells per field in corneal sections (from 11.3±5.29 to 2.0±1.90) (P <0.01), and reduced the formation of corneal neovascularization and neovascular lymphatic vessels (by 76.86% and 71.16%, respectively, both P <0.001). Conclusion: Topical use of tocilizumab to inhibit IL-6 showed no significant corneal toxicity and can regulate the repair of cornea after alkali burns.
目的：探究间歇性禁食(intermittent fasting, IF)对内毒素诱导小鼠葡萄膜炎(endotoxin-induced uveitis, EIU)的保护作用及其可能的抗炎机制。方法：小鼠随机分为对照组(Ctr)、EIU组及IF+EIU组。16∶8禁食方案(9 : 00—17 : 00进食)。对照组行玻璃体腔内注射磷酸盐缓冲溶液(phosphate buffered saline, PBS)，其余两组行玻璃体腔内脂多糖注射。建模后监测小鼠空腹血糖及体质量。光学相干断层扫描和苏木精伊红染色观察评估炎症水平。视网膜铺片行神经炎症相关的观察评价。BV2细胞分为Ctr组，LPS组及饥饿+内毒素组，蛋白印迹及实时荧光定量逆转录PCR技术检测相关蛋白及mRNA表达水平。结果：①IF对体质量无明显影响，可引起血糖显著降低随后逐渐恢复。病程中期起IF干预下小鼠视网膜水肿恢复，玻璃体腔内炎性渗出比EIU组显著减少(P＜0.01)。IF逆转LPS诱导的小胶质细胞激活，减轻视网膜神经节细胞及神经纤维损伤(P＜0.05)。②饥饿培养抑制LPS诱导的BV2细胞的磷酸化信号转导与转录激活因子1和3及诱导型一氧化氮合酶( inducible nitric oxide synthase, iNOS)的蛋白表达水平(P＜0.05)，显著降低iNOS、白介素-6等炎症因子的表达水平。结论：IF能够加速EIU炎症的消退，减轻组织结构的炎性破坏，抑制小胶质细胞的促炎型激活。
Objective: To investigate the protective effects of intermittent fasting (IF) on endotoxin-induced uveitis in mice and its potential anti-inflammatory mechanisms. Methods: Mice were randomly divided into three groups: control group (Ctr), endotoxin-induced uveitis (EIU) group, and IF + EIU group. The IF regimen followed a 16:8 fasting scheme (feeding from 9:00 to 17:00). The control group received intravitreal injections of PBS, while the other two groups received intravitreal injections of lipopolysaccharide (LPS). After modeling, fasting blood glucose and body weight of the mice were monitored. Inflammation levels were assessed using OCT and H&E staining. Retinal flat mounts were used for evaluating neuroinflammation. BV2 cells were divided into Ctr group, LPS group, and starvation (LG) + LPS group. The expression levels of related proteins and mRNA were detected using WB and RT-qPCR. Results: IF had no significant effect on body weight but caused a significant decrease in blood glucose, which gradually recovered. From the middle stage of the disease, mice in the IF intervention group show edretinal edema recovery, significantly reduced intravitreal inflammatory exudation and cell infiltration compared to the EIU group (P <0.01). IF reversed LPS-induced microglial activation and significantly alleviated damage to retinal ganglion cells and nerve fibers (P <0.05). Starvation culture significantly inhibited LPS-induced expression levels of p-STAT1/3 and iNOS proteins in BV2 cells (P <0.05) and significantly reduced the expression levels of inflammatory factors such as iNOS and IL-6. Conclusion: IF can accelerate the resolution of EIU inflammation, reduce inflammatory damage to tissue structures, and inhibit pro-inflammatory activation of microglia.
糖尿病视网膜病变(diabetes retinopathy, DR)是糖尿病常见的眼部并发症，其病理过程复杂，涉及多种细胞及炎症因子。Müller细胞作为视网膜主要支持细胞，在DR中不仅产生白介素-17(interleukin-17, IL-17)，还作为其主要靶点发挥作用，通过谷氨酸代谢异常、血管内皮生长因子(vascular endothelial growth factor, VEGF)分泌增加及调控参与DR的病理过程，加重炎症反应。IL-17主要由辅助性T细胞17(T helper cell 17, Th17)分泌，通过促进多种炎症介质(如细胞因子、趋化因子和金属蛋白酶)的分泌，增强炎症反应，导致视网膜微血管损害和神经元凋亡，促进DR的发展。高糖环境下，Müller细胞功能受损，IL-17进一步加剧其功能障碍形成恶性循环。研究表明，阻断IL-17及核因子-κB激活剂1(Nuclear factor-kappa B activator 1, Act1)/肿瘤坏死因子受体关联因子6(tumor necrosis factor receptor associated factor 6, TRAF6)/核因子-κB(Nuclear factor-kappa B, NF-κB)信号通路可减轻DR的病理改变，为DR的治疗提供了新的思路。因此，深入研究IL-17与Müller细胞在DR中的相互作用机制，对于研究该疾病的发病机制及开发精准有效的治疗策略具有重要意义。
Diabetes retinopathy (DR) is a common ocular complication of diabetes, characterized by a complex pathological process involving multiple cells and inflammatory factors. Müller cells, as the primary supporting cells of the retina, not only produce interleukin-17 (IL-17) but also serve as a primary target in DR. They participate in the pathological process of DR by contributing to abnormal glutamate metabolism, increased secretion of vascular endothelial growth factor (VEGF), and regulatory functions, thereby exacerbating the inflammatory response. IL-17 is primarily secreted by T helper cell 17 (Th17) cells and enhances the inflammatory response by promoting the secretion of various inflammatory mediators (such as cytokines, chemokines, and metalloproteinases), leading to retinal microvascular damage and neuronal apoptosis, which accelerates the progression of DR. In a high-glucose environment, Müller cell function is impaired, and IL-17 further exacerbates this dysfunction, creating a vicious cycle. Studies have shown that blocking the IL-17 and Act1/TRAF6/NF-κB signaling pathways can mitigate the pathological changes associated with DR, providing new insights for the treatment of this disease. Therefore, conducting in-depth research on the interaction mechanism between IL-17 and Müller cells in DR is of great significance for exploring the pathogenesis of this disease and developing precise and effective treatment strategies.
神经营养性角膜病变是一种与角膜神经退行性改变有关的疾病，表现为角膜神经的知觉和营养功能受损，导致角膜上皮缺损、角膜溃疡和角膜穿孔。目前对神经营养性角膜病变的主要治疗方式有药物治疗、非手术干预治疗和手术治疗，但是对于重度病变患者行药物治疗、非手术干预治疗通常效果不佳。对未恢复角膜神经营养功能的患者行角膜移植术，可能导致角膜移植术后上皮持续不愈合，因此恢复角膜神经营养功能是该类患者复明的重要前提。角膜神经移植术是重度神经营养性角膜病变患者恢复角膜神经营养功能，提高角膜知觉，改善角膜透明度的重要和有效的治疗方法。角膜神经移植术通过将具有正常功能的供体神经移植到麻痹眼角膜缘周围，使神经末梢重新长入角膜基质，恢复角膜知觉功能。随着角膜神经移植术的术式的不断改进，其良好的术后效果和优点已经渐渐凸显。文章基于作者结合团队在角膜神经移植术方面经验结合近年研究进展阐述了神经营养性角膜病变的治疗手段和不同术式在角膜神经移植术中的应用，并进行展望。
Neurotrophic keratopathy is a disease related to degenerative changes in corneal nerves, resulting in impaired sensory and nutritive functions of corneal nerves. This leads to corneal epithelial defects, corneal ulcers, and corneal perforation. Currently, the main treatment modalities include pharmacotherapy, non-surgical interventions, and surgical treatment. However, drug therapy and non-surgical interventions often yield unsatisfactory results for severe neurotrophic keratopathy patients. Performing corneal transplantation in patients with unrecovered corneal sensation may result in persistent epithelial defect. Therefore, the restoration of corneal sensation is a crucial prerequisite for visual rehabilitation. Corneal neurotization emerges as an important and effective therapeutic approach for severe cases of neurotrophic keratopathy, aiming to restore corneal sensation and enhance corneal transparency. The procedure involves transplanting nerves from a donor with normal sensory function to the paralyzed sub-Tenon perilimbal space, allowing nerve endings to regenerate into the corneal stroma and restoring corneal sensory function. With continuous improvements in the technique of corneal neurotization, its favorable postoperative outcomes and advantages are becoming increasingly evident. This article, based on the team's experience in corneal neurotization, elaborates on the treatment modalities for neurotrophic keratopathy and the application and prospects of various surgical techniques in corneal neurotization.
目的：结合眼科住院医师规范化培训(住培)的特点，建立基于钉钉平台的全面质量管理模式(total quality management, TQM)，探索一种高效的顺应时代特征的眼科教学管理模式。方法：研究团队依托中山大学中山眼科中心，选取82名眼科四证合一的住培一年级的学生作为研究对象，并将其随机分为两组，试验组41人采用基于钉钉平台的TQM模式进行全过程教学管理，采用全员参与、全程跟踪、全面评价的管理模式以保障教学质量。对照组41人接受传统的教学管理模式。观察指标为两组间教学前后测试分数、教学后满意度调查的问卷得分等。结果：通过对两组学生进行课前课后的测试，TQM模式组相较于传统模式组在学习成绩有所提升，课前课后分数的差值分别为40(30,40)分和30(20,50)分，比较差异有统计学意义(P =0.031)。问卷调查结果显示，两组满意度总分比较差异无统计学意义[10(10,10) 分 vs. 10(9,10)分，P =0.207]，但在满意度分项内容掌握性上，TQM模式组分值高于传统模式组[5(5,5)分 vs. 5(4,5)分，P =0.046]。结论：基于钉钉平台的TQM模式在眼科教学中能够有效提高住培的教学质量与学生满意度，相比传统教学管理模式具有更大的教学优势，可为眼科住培提供了一种创新且实用的教学管理模式，对于培养适应时代需求的高水平眼科医师具有重要意义。
Objective: To combine the characteristics of standardized training for ophthalmic resident physicians, establishes a Total Quality Management (TQM) model based on the DingTalk platform, and explored an efficient ophthalmic teaching management model that adapts to the characteristics of the times. Methods: The research team, based at Zhongshan Ophthalmic Center, selected 82 first-year postgraduate students undergoing the national standardized training for resident doctors (STRD) as participants, randomly allocating them into two groups. The experimental group consisting of 41 trainees received TQM-modeled online learning via the DingTalk platform, adopting a management model of full participation, full process tracking, and comprehensive evaluation to ensure teaching quality. While the control group, also comprising 41 trainees, underwent traditional offline instruction. The TQM group engaged in live streaming lectures on the DingTalk platform, whereas the conventional group continued with face-to-face teaching in classroom. Data including pre- and post-teaching scores, as well as scores from satisfaction surveys are analyzed. Results: Comparing pre- and post-teaching scores, significant statistical differences were found between the TQM and traditional groups, with mean score improvements of 40(30,40) points and 30(20,50) points, respectively, indicating statistical significance (P =0.013). Furthermore, the questionnaire survey revealed that the TQM group scored higher than the traditional group in aspects such as course design, clinical relevance, content mastery, and instructor satisfaction. In addition, the questionnaire survey showed that there was no statistically significant difference in the total satisfaction score between the two groups (10(10,10) points vs. 10(9,10)points P =0.207), but in terms of mastery of satisfaction sub items, the TQM model group scored higher than the traditional model group (5(5,5) points vs. 5(4,5) points, P =0.046). Conclusions: The application of a TQM-based model on the DingTalk platform significantly enhances the teaching quality and student satisfaction in the residency training of ophthalmologists, demonstrating greater pedagogical advantages over traditional methods. This efficient ophthalmic teaching management model thus provides a promising solution for standardized residency training in ophthalmology, and holds considerable importance for nurturing highly competent ophthalmologists who can meet the demands of the current era.
目的：应用广角扫频源光学相干断层扫描成像(swept-source optical coherence tomography, SS-OCT)的en face结构投射图研究玻璃体早期液化特征。方法：使用SS-OCT进行18 mm×18 mm 的容积（Cube）扫描，创建并分析健康未成年人（年龄5~18岁）70眼的系列玻璃体en face结构投射图。 结果：在未成年人中，视网膜前的玻璃体包含4种液化结构，分别为后皮质前玻璃体囊袋（posterior precortical vitreous pocket, PPVP）、视盘前Martegiani区（the area of Martegiani, AM）、血管前液化裂隙（prevascular vitreous fissures，PVF）和液化池（cistern）。所有研究眼均能检出PPVP、AM和PVF，其中22眼（31.4%）的PPVP和AM连通。41眼（58.6%）可检出液化池，且其年龄大于未检出液化池的个体（P =0.01），液化池的发生与年龄呈正相关（rs=0.315，P =0.008）。液化池的象限空间分布频率依次为颞上（90.2%）、鼻上（58.5%）、颞下（36.6%）、鼻下（24.4%），最常累及颞上象限（P＜0.001）。 结论：PPVP、AM和PVF是健康人群视网膜前玻璃体早期液化过程中均出现的特征。液化池的发生与年龄呈正相关，最常出现在颞上象限，可能是年龄相关性玻璃体液化变性的结果。
Objective: To investigate the early vitreous liquefaction characteristics using en face structural projection images obtained by wide-angle swept-source optical coherence tomography (SS-OCT). Methods: SS-OCT was employed to perform 18*18mm volumetric (Cube) scans. A series of en face structural projection images of the vitreous were created and analyzed for 70 eyes from healthy minors aged between 5 and 18 years. Results: In minors, four types of vitreous liquefaction structures were identified anterior to the retina: pre-posterior vitreous pocket (PPVP), the preoptic area of Martegiani (AM), pre-vascular liquefaction fissures (PVF), and cisterns. PPVP, AM, and PVF were detectable in all studied eyes, with PPVP and AM being interconnected in 22 eyes (31.4%). Cisterns were observed in 41 eyes (58.6%), and the mean age of individuals with cisterns was higher than those without (P =0.01). The occurrence of cisterns positively correlated with age (r=0.315; P=0.008). The frequency of cistern quadrant distribution was highest in the superotemporal quadrant (90.2%), followed by the superonasal quadrant (58.5%), inferotemporal quadrant (36.6%), and inferonasal quadrant (24.4%). The superotemporal quadrant was the most frequently affected (P <0.001). Conclusion: PPVP, AM, and PVF are features consistently observed in the early vitreous liquefaction process anterior to the retina in healthy individuals. The occurrence of cisterns positively correlates with age and is most common in the superotemporal quadrant, possibly representing the result of age-related vitreous liquefaction degeneration. These findings provide a theoretical foundation for studying the pathogenesis of vitreoretinal interface diseases.
