传统的眼底手术要求眼科医生具备精细的操作技术，但即便拥有再精湛的操作技术，眼底手术还是存在很大的风险性。因此，为了减少手术风险，提高手术质量，对传统眼底手术进行改进是十分必要的。近年来，在我国对于人工智能产业的大力支持之下，应用于各类行业的机器人随之诞生。机器人辅助系统(robot auxiliary system，RAS)在医学领域，特别是眼科学中应用广泛。对近几年RAS应用于眼底手术的案例进行整理总结，并将RAS参与的眼底手术以及传统的眼底手术进行对比，可以发现RAS在眼底手术中的应用可以显著提高手术效率，并降低手术风险。未来RAS的发展趋势可能着重聚焦于与深度学习算法的紧密结合。通过算法对手术中的视野图像进行预测、优化，从而让高精度的眼底手术更加高效、安全。
Traditional fundus surgery requires ophthalmologists to be equipped with sophisticated operating techniques, but even with the most sophisticated operating techniques, fundus surgery still has great risks. Therefore, in order to reduce the risk of surgery and improve the quality of surgery, it is very necessary to improve the traditional fundus surgery. In recent years, with China’s strong support for the artificial intelligence industry, robots used in various industries have been born. Robot auxiliary system (RAS) is widely used in the medical field, especially in ophthalmology. By summarizing the cases of fundus surgery with RAS in recent years and comparing the fundus surgery involving RAS with traditional fundus surgery, it can be found that the application of RAS in fundus surgery can significantly improve the efficiency of surgery and reduce the risk of surgery. The future development trend of RAS may focus on the close integration with deep learning algorithms, which can predict and optimize the field of view images during surgery so that high-precision fundus surgery can be more efficient and safer.
视盘内出血伴视盘旁视网膜下出血(intrapapillary hemorrhage with adjacent peripapillary subretinal hemorrhage, IHAPSH)的病例报道较为少见。此病好发于患有轻、中度近视的中青年，且伴有视盘向倾斜或小视盘的患者，具有自限性，视力预后良好，无后遗症，而且很少复发。IHAPSH的眼底表现为视盘内出血、视盘旁视网膜下出血，严重者可出现玻璃体积血。文章报道一例IHAPSH，患者为26岁中度近视女性，主要症状为左眼无痛性视力下降伴眼前黑影飘动6 d。双眼最佳矫正视力均为1.0。眼底检查发现双眼视盘偏小，呈倾斜位，右眼视盘鼻侧见红色视网膜下出血灶；左眼视盘内及视盘鼻侧、上方、颞上方视网膜浅层出血，视盘鼻侧见边界清晰的新月形红色视网膜下出血。未进行特殊治疗，2个月后出血完全吸收。此病病因复杂多样，需与多种眼底疾病相鉴别，及时行眼科相关检查以排除其他原因导致的视盘水肿、视盘出血。文章通过文献回顾，总结其临床特征、发病机制、诊断、鉴别诊断、治疗及预后。
Intrapapillary hemorrhage with adjacent peripapillary subretinal hemorrhage (IHAPSH) is rarely reported. IHAPSH commonly affects young myopic eyes with tilted optic discs and spontaneously resolves without treatment, with an excellent prognosis for vision recovery and very rarely recur. The fundus manifestations of IHAPSH are intrapapillary hemorrhage, peripapillary subretinal hemorrhage, or even with vitreous bleeding. An 26-year-old female with mild myopia presented with symptoms of blurry vision and black filamentous floaters for 6 days. Her BCVA was 1.0 in both eyes. Fundus examination showed that both discs appear small, and elevated in the nasal regions. Intrapapillary hemorrhage, peripapillary subretinal hemorrhage and vitreous hemorrhage were observed in the left eye, while only peripapillary subretinal hemorrhage was seen in the right eye. The hemorrhage was resolved spontaneously without any complication after 2 months. The etiology of IHAPSH is complex, and it should be differentiated from other causes of papilledema and disc hemorrhage. The clinical characteristics, pathogenesis, diagnosis, differential diagnosis, treatment and prognosis were summarized through the literature review.
Aims: To explore the point-wise correlations between 10-2 visual field (VF) metrics and macular vessel density, as measured by optical coherence tomography angiography (OCTA), in patients with early open-angle glaucoma (OAG) and healthy controls. Methods: This is a cross-sectional study that retrospectively analyzed data from 54 participants (18 eraly OAG patients and 36 healthy controls) from the Zhongshan Ophthalmic Center. All participants underwent comprehensive ophthalmic examinations, 10-2 VF, and macular OCTA imaging. The correlation between capillary density (CD) in macular subregions and light sensitivity (LS) at corresponding VF test points was analyzed using Pearson's correlation coefficients. Results: The analysis revealed a significant reduction in CD within the inferior macular regions of glaucomatous eyes. Notably, there were strong point-wise correlations between CD and 10-2 VF, particularly in the inferior region of outer ring (peak r = 0.534, P < 0.001). Conclusion: The point-wise correlation between 10-2 VF and macular CDdemonstrates the potential for using CD to predict central VF damage in glaucoma, emphasizing theimportance of macular microcirculation in early disease screening.
Aims: To explore the point-wise correlations between 10-2 visual field (VF) metrics and macular vessel density, as measured by optical coherence tomography angiography (OCTA), in patients with early open-angle glaucoma (OAG) and healthy controls. Methods: This is a cross-sectional study that retrospectively analyzed data from 54 participants (18 early OAG patients and 36 healthy controls) from the Zhongshan Ophthalmic Center. All participants underwent comprehensive ophthalmic examinations, 10-2 VF, and macular OCTA imaging. The correlation between capillary density (CD) in macular subregions and light sensitivity (LS) at corresponding VF test points was analyzed using Pearson's correlation coefficients. Results: The analysis revealed a significant reduction in CD within the inferior macular regions of glaucomatous eyes. Notably, there were strong point-wise correlations between CD and 10-2 VF, particularly in the inferior region of outer ring (peak r = 0.534, P < 0.001). Conclusion: The point-wise correlation between 10-2 VF and macular CDdemonstrates the potential for using CD to predict central VF damage in glaucoma, emphasizing theimportance of macular microcirculation in early disease screening.
目的：探究可弯曲喉罩在经鼻内镜眼科日间手术中应用的安全性。方法：收集2023年1月—2024年1月在全身麻醉(全麻)下行经鼻内镜眼科日间手术成年患者资料，分析可弯曲喉罩使用的成功率，观察患者入室时、插管后、手术开始时、手术结束时的血流动力学变化情况；并记录喉罩置入后、手术开始5 min、手术开始30 min和手术结束时的呼吸参数及患者在麻醉恢复室（post-anesthesia care unit，PACU的停留期间的并发症。结果：共635例患者纳入分析，其中619例患者选用喉罩，607例患者喉罩置入成功，成功率98.1%，喉罩置入失败12例，均为诱导期间置入失败，占1.9%，无术中发生喉罩通气失败改气管插管病例。喉罩通气能满足经鼻内镜手术需求，表现为各时点通气量无显著变化及平稳的心率和平均动脉压。患者均顺利复苏，PACU停留时间为(34.6±11.2) min，喉罩拔除时间为(14.3±4.3) min，无二次气管内插管事件发生。结论：置入成功的可弯曲喉罩可安全应用在经鼻内镜眼科日间全麻手术中。
Objective: To investigate the safety of flexible laryngeal masks in the application of endoscopic ophthalmic ambulatory surgery. Methods: Data of adult patients undergoing endoscopic day ophthalmic surgery under general anesthesia from January 2023 to January 2024 were collected; the changes in hemodynamics at T1 (entry into the operating room), T2 (after intubation), T3 (before surgery), and T6 (after surgery) time points and the respiratory parameters at T2 (after intubation), T4 (5 minutes after surgery), T5 (30 minutes after surgery), and T6 (after surgery) time points were analyzed; meanwhile, the complications during the PACU stay were also analyzed. Results: A total of 635 patients were included in the retrospective analysis, of whom 619 patients were initially used FLMA, FLMA were successfully inserted in 607 patients with a rate of 98.1% while 12 patients suffered insertion failure during the period of anesthesia induction. Importantly, none of patients displayed FLMA ventilation failure and required tracheal intubation during the period of surgery. General anesthesia via FLMA ventilation can provide high quality of surgical field for endoscopic ophthalmic surgery, as evidenced by stable heart rates and mean arterial pressure and no significant change in minute ventilation at each time points. All patients recovered uneventfully with a PACU stay time of 34.6±11.2 min and FLMA removal time of (14.3±4.3) min. None of patients exhibited subsequently endotracheal intubation after FLMA removal. Conclusion: FLMA with successful placement can be safely used for endoscopic ophthalmic ambulatory surgery under general anesthesia.
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：开发一款可自动校准测试距离的智能手机视力检测APP(WHOeye的iOS版本)，并评估其实用性。方法： WHOeyes在经过验证的视力检测APP “V@home”的基础上新增自动距离校准(automatic distance calibration, ADC)功能。研究招募了3组不同年龄(≤20岁、20~40岁、>40岁)的中国受试者，分别使用糖尿病视网膜病变早期治疗研究(Early Treatment Diabetic Retinopathy Study, ETDRS)视力表和WHOeyes进行远距离和近距离的视力检测。ADC功能用于确定WHOeyes的测试距离。红外测距仪用于确定ETDRS的测试距离以及WHOeyes的实际测试距离。通过问卷调查评估用户满意度。结果：WHOeyes ADC确定的实际测试距离在3个年龄组中均与预期测试距离总体上表现出良好的一致性(P > 0.50)。在远距离和近距离视力检测方面，WHOeyes的准确性与ETDRS相当。WHOeyes与ETDRS之间的平均视力差异范围为–0.084 ~ 0.012 logMAR，各组的二次加权卡帕系数(quadratic weighted kappa, QWK)均大于0.75。WHOeyes在近距离和远距离视力检测中的重测信度高，平均差异范围为–0.040 ~ 0.004 logMAR，QWK均大于0.85。问卷调查显示WHOeyes具有较好的用户体验和接受度。结论：与金标准ETDRS视力表方法相比，WHOeyes测试距离较为准确，可以提供准确的远距离和近距离视力测量结果。
Background: To develop and assess usability of a smartphone-based visual acuity (VA) test with an automatic distance calibration (ADC) function, the iOS version of WHOeyes. Methods: The WHOeyes was an upgraded version with a distinct feature of ADC of an existing validated VA testing APP called V@home. Three groups of Chinese participants with different ages (≤20, 20-40, >40 years) were recruited for distance and near VA testing using both an Early Treatment Diabetic Retinopathy Study (ETDRS) chart and the WHOeyes. The ADC function would determine the testing distance. Infrared rangefinder was used to determine the testing distance for the ETDRS, and actual testing distance for the WHOeyes. A questionnaire-based interview was administered to assess satisfaction. Results: The actual testing distance determined by the WHOeyes ADC showed an overall good agreement with the desired testing distance in all three age groups (p > 0.50). Regarding the distance and near VA testing, the accuracy of WHOeyes was equivalent to ETDRS. The mean difference between the WHOeyes and ETDRS ranged from -0.084 to 0.012 logMAR, and the quadratic weighted kappa (QWK) values were greater than 0.75 across all groups. The test-retest reliability of WHOeyes was high for both near and distance VA, with a mean difference ranging from -0.040 to 0.004 logMAR and QWK all greater than 0.85. The questionnaire revealed an excellent user experience and acceptance of WHOeyes. Conclusion: WHOeyes could provide accurate measurement of the testing distance as well as the distance and near VA when compared to the gold standard ETDRS chart.
目的：通过高通量测序分析进行基因诊断，鉴别视网膜病变中的神经纤维瘤病，为其早诊早治提供重要依据。方法：回顾性分析眼遗传病高通量测序数据库中的NF1和NF2基因变异，根据ACMG/AMP指南解析变异致病性；进一步结合患者的临床表型、家族史以及其他检查结果，综合判断明确是否患有神经纤维瘤病，同时进行疾病的进展和随访的研究分析。结果：通过分析不同眼部表型家系的高通量测序结果，共在11例先证者中发现NF1和NF2基因的10个可能致病变异，包括7个NF1变异和3个NF2变异。这11例先证者的初始诊断包括家族性渗出性玻璃体视网膜病变、黄斑/视网膜发育不良、斜视、视网膜色素变性、Coats病和牵牛花综合征等。其中，在1例初诊为家族性渗出性玻璃体视网膜病变的患儿中，检测到3个基因的致病变异，即NF2: c.122G>A/p.(W41*)、RS1: c.520C>T/p.(R174W)和NYX: c.1027C>T/p.(R343C)。随访检查发现，该患儿的复杂眼部表型符合NF2、RS1和NYX致病变异的临床改变，且MRI检查发现双侧前庭神经鞘瘤、脊髓室管膜瘤和多发性神经鞘瘤改变。除该患者外，还有4例患者在随访中发现存在牛奶咖啡斑或雀斑样色素沉着等皮肤改变，1 例合并小脑神经纤维瘤浸润。结论: 高通量测序分析能有效检测出神经纤维瘤病相关基因的变异，有助于筛选非典型表现的神经纤维瘤病，为疾病的早期诊断，尤其是对严重中枢神经系统病变的早期筛查和及时干预，提供了重要依据。
Objective: To identify neurofibromatosis in retinopathy through high-throughput sequencing analysis and provide important indicators for early diagnosis and treatment. Methods: Variants in NF1 and NF2 were selected from in-house high-throughput sequencing, including targeted exome sequencing, exome sequencing and whole genome sequencing, of individuals with different eye conditions. Pathogenic or likely pathogenic variants were assessed according to ACMG/AMP criteria. All the available clinical data, including clinical manifestation, family history and other examination results, were summarized and further analyzed to determine whether neurofibromatosis. Results: Based on the results of in-house high-throughput sequencing, a total of ten pathogenic or likely pathogenic variants in NF1 and NF2 were identified in 11 unrelated cases with various eye conditions, including three NF2 variants in four cases and seven NF1 variants in seven cases. The unrelated cases with NF1 and NF2 variants had initial clinical manifestation similar to familial exudative vitreoretinopathy (FEVR), macular or retinal dystrophy, strabismus, retinitis pigmentosa, Coats disease, or morning glory syndrome. In one of these cases, who was diagnosed as FEVR at the initial visit, three pathogenic variants of three different genes were identified, namely NF2: c.122G>A/p.(W41*), RS1: c.520C>T/p.(R174W) and NYX: c.1027C>T/p.(R343C). Follow-up examination on this case revealed a complex retinopathy, which were consistent with clinical presentations due to pathogenic variants in NF2, RS1, and NYX, as well as bilateral vestibular schwannomas, spinal ependymoma and multiple schwannomas by MRI. In addition to this patient, a follow-up examination on four of the seven cases present Café-au-lait macules or freckling, which could be easily neglected if neurofibromatosis is not realized on the initial visit, while one had neurofibromatosis in cerebellum. Conclusions: Complex retinopathy may present as the initial sign of neurofibromatosis, and high-throughput sequencing analysis for neurofibromatosis related genes contribute to early diagnosis of neurofibromatosis and facilitating early identification of vital systemic complication.
青光眼是一组以视盘萎缩凹陷、视野缺损以及视力下降为共同特征的视神经退行性疾病，也是世界首位不可逆性致盲眼病，导致患者生活质量降低、引起极大卫生经济负担。但其发病机制尚不明确，促进房水排出从而降低眼内压仍是目前减缓疾病进展的唯一治疗手段。房水排出的主要途径是经由小梁网进入Schlemm's管最后汇入巩膜外静脉，因此小梁网在调节房水排出以及平衡眼内压方面发挥重要作用。近年来，体内以及体外房水排出测量技术和小梁网成像技术不断突破，众多研究表明小梁网存在压力依赖的节律性搏动，在房水的脉冲式排出中起到关键作用，但在青光眼中这种搏动随疾病的进展减弱甚至消失。文章以小梁网的泵理论为核心，总结青光眼中房水排出的最新研究进展，并从恢复小梁网功能的角度出发探索可能有效的治疗策略，为青光眼的临床诊治提供新的思路。
Glaucoma, a group of optic nerve degenerative diseases, is characterized by papillary atrophy, visual field defects, and decreased vision. It is also the leading cause of irreversible blindness worldwide, significantly reducing patients’ the quality of life of patients and posing considerable health economic burdens. However, the pathogenesis of glaucoma remains unclear, and promoting aqueous humor outflow to reduce intraocular pressure is the only treatment option available to slow disease progression. The main pathway for aqueous humor outflow is through the trabecular meshwork into Schlemm's canal and finally into the episcleral veins, highlighting the crucial role of the trabecular meshwork in regulating aqueous humor outflow and maintaining intraocular pressure balance. In recent years, there have been notable breakthroughs in in vivo and in vitro aqueous humor outflow measurement techniques and trabecular meshwork imaging technologies.Many studies suggest that the trabecular meshwork exhibits pressure-dependent rhythmic pulsation, playing a crucial role in the pulse-like outflow of aqueous humor. Unfortunately, in glaucoma, this pulsation weakens or even disappears as the disease progresses. This article focuses on the trabecular meshwork's pump theory and summarizes the latest research progress in aqueous humor outflow in glaucoma, exploring potential effective therapeutic strategies aimed at restoring trabecular meshwork function. This provides new insights for the clinical diagnosis and treatment of glaucoma.
目的：开发细胞级高分辨率、结构与功能一体化的双模态全视场光学相干层析系统(full-field optical coherence tomography,FFOCT)，实现角膜缘组织的双模态FFOCT成像。方法：基于Linnik干涉成像原理，利用高数值孔径显微物镜(NA=0.8)及高速平面互补金属氧化物半导体(complementary metal oxide semiconductor,CMOS)相机，设计搭建高分辨率的组织静态结构和内源动态功能成像一体化双模态FFOCT系统；构建基于四相位调制结构影像提取及时域干涉信号动态频谱分析的功能影像重建算法；对人供体角膜缘组织开展各深度层的双模式FFOCT成像有效性验证。结果：搭建的双模态FFOCT成像系统可实现横向分辨率0.5 μ m，轴向分辨率1.7 μ m，成像视野320 μ m×320 μ m，相机采集速度100 Hz。系统实现角膜缘组织无外源标记情况下的细胞级分辨率三维结构和内源功能成像，FFOCT静态结构影像清晰显示角膜缘上皮、Vogt栅栏、隐窝、基质、血管及淋巴管等结构，FFOCT动态功能影像突出显示了代谢活跃细胞(角膜缘上皮细胞、免疫细胞等)。结论：双模态FFOCT高分辨率成像系统可提供角膜缘微观结构和活细胞无标记内源功能可视化信息，将为角膜缘疾病的研究及临床诊疗提供全新的成像分析技术。
Objective: To develop a cellular-level, high-resolution, integrated dual-modal full-field optical coherence tomography (FFOCT) system capable of simultaneously imaging the structure and function of limbus tissue. Methods: Utilizing the Linnik interference imaging principle, a high-resolution dual-modal FFOCT system was designed and constructed using a high numerical aperture (NA=0.8) microscope objective and a high-speed flat CMOS camera. A functional imaging reconstruction algorithm based on four-phase modulation structure image extraction and dynamic frequency spectrum analysis of temporal interference signals was developed. The effectiveness of dual-mode FFOCT imaging at various depth layers of human corneal limbal tissue was validated. Results: The constructed dual-modal FFOCT imaging system achieved lateral resolution of 0.5 μ m, axial resolution of 1.7 μ m, imaging field of view of 320 μ m × 320 μ m, and camera acquisition speed of 100 Hz. The system enabled cellular-level resolution three-dimensional structural and intrinsic functional imaging of corneal limbal tissue without exogenous labeling. Static structural FFOCT images clearly displayed limbal epithelium, palisades of Vogt, crypts, stroma, blood vessels, and lymphatic vessels, while dynamic functional FFOCT images highlighted metabolically active cells (limbal epithelial cells, immune cells, etc.). Conclusion: The dual-modal FFOCT high-resolution imaging system provides visualization of corneal limbal microstructural and live cell intrinsic functional information without labeling, offering a novel imaging analysis technique for research and clinical diagnosis and treatment of limbal diseases.
目的：利用双向孟德尔随机化方法(mendelian randomization,MR)探索骨关节炎与青光眼的潜在因果关系。方法：使用全基因组关联研究(genome-wide association studies,GWAS)数据，挑选出与骨关节炎和青光眼高度相关的单核苷酸多态性(single nucleotide polymorphism,SNP)作为工具变量。本研究以逆方差加权法(inverse variance weighted,IVW)作为主要的分析手段，以加权中位数法、加权模型法、简单众数法及MR-Egger回归法作为辅助方法，采用F统计量、Cochran Q检验、MR Egger截距测试、留一法(leave one out)及多效性残差和离群值法(mendelian randomization pleiotropy RESidual sum and outliers,MR-PRESSO)进行敏感性分析。本研究采用比值比(odds ratio,OR)作为主要的效应量度指标，以95%置信区间(confidence interval,CI)评估关联强度，探讨骨关节炎与青光眼的双向因果关系。结果：IVW结果表明骨关节炎可增加青光眼的患病风险(95%CI: 1.00~1.20，OR=1.10，P=0.043)，辅助方法的结果显示了相同的因果方向，但无统计学意义。在反向MR分析中，IVW结果表明，青光眼不会增加患骨关节炎的风险(OR=1.02，95%CI: 0.97~1.08)，4种辅助方法均支持IVW结果。所选SNP的F统计量均超过10，无弱工具变量。Cochran Q检验、MR-Egger截距检验以及MR-PRESSO分析结果均未显示所选SNP之间存在异质性或水平多效性。反向MR分析结果显示Cochran Q检验有异质性，但未发现水平多效性。留一法结果显示没有对整体分析结果产生了显著影响的SNP。结论：正向MR分析表明骨关节炎可能会增加患青光眼的风险，二者之间存在正相关。反向MR分析结果表明，青光眼对骨关节炎无因果效应。
Objective: To investigate the potential bidirectional causal association between osteoarthritis and glaucoma through the application of bidirectional Mendelian randomization (MR). Methods: Instrumental variables were selected in this study based on single nucleotide polymorphisms (SNP) strongly associated with osteoarthritis and glaucoma, as utilizing genome-wide association studies (GWAS) data. The inverse variance weighting (IVW) method was served as the primary analytical approach, while the weighted median mode, simple plurality and MR-Egger regression methods were employed as complementary methods. Sensitivity analyses were conducted using F-statistic, Cochran Q-test, MR Egger's intercept test, leave-one-out, and multiplicity of residuals and outliers method (MR-PRESSO). The ratio of odds ratios (OR) was adopted as the primary effect estimate, and the strength of association was evaluated by 95% confidence interval (CI) to explore the bidirectional causal relationship between osteoarthritis and glaucoma. Results: The IVW analysis revealed that osteoarthritis elevates the risk of glaucoma with an odds ratio of (OR) of 1.10(95% CI: 1.00-1.20). While the adjunctive methods concurred with this causal direction, their findings did not reach statistical significance. In contrast, the inverse Mendelian randomization (MR) analysis utilizing the inverse variance weighting method demonstrated that glaucoma does not enhance the risk of developing osteoarthritis (OR=1.02, 95% CI: 0.97-1.08). This conclusion was upheld by all four auxiliary methods. The F-statistic values for the selected SNP exceeded 10, indicating the absence of weak instrumental variables. Furthermore, the Cochran Q test, MR-Egger intercept test, and MR- PRESSO analyses revealed no evidence of heterogeneity or horizontal pleiotropy among the SNP. However, the inverse MR analysis displayed heterogeneity in the Cochran Q test, yet no horizontal pleiotropy was detected. The leave-one-out method analysis identified no significant influence of any individual SNP on the overall results. Conclusions: Forward MR analyses indicated that osteoarthritis may serve as a risk factor for glaucoma, indicating a positive correlation between the two conditions. Conversely, reverse MR analysis failed to establish a causal link between glaucoma and osteoarthritis.
