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.

作为一种新型无创且操作简单的主观检查手段，临界闪烁融合频率(critical flicker fusionfrequency,CFF)可动态反映人眼视功能变化情况。作为早期识别脱髓鞘病变和评估视功能恢复情况的敏感指标，上个世纪已被国外学者用于视网膜和视神经疾病研究中，包括氯喹中毒性视网膜病变、糖尿病视网膜病变、中心性浆液性视网膜病变、年龄相关的黄斑病变、乙胺丁醇中毒性视神经病变、视神经炎和非动脉炎性前部缺血性视神经病变。在视网膜和视神经疾病中，CFF均有不同程度下降，依据CFF改善程度以及主要损害的色光可能有助于视网膜和视神经疾病的鉴别，且CFF与其他视功能，视力、视野、视觉诱发电位的潜时具有较好的相关性。目前国内相关研究尚处于起步阶段，本文就CFF在视网膜和视神经疾病的应用情况做一总结。

As a new non-invasive and simple subjective examination method, critical flicker fusion frequency (CFF) can dynamically reflect the changes of visual function of human eyes. As a sensitive indicator for early identification of demyelinating diseases and assessment of visual function recovery, it has been used by foreign scholars in the last century in the field of retinal and optic nerve diseases, including chloroquine toxic retinopathy, diabetic retinopathy, central serous retinopathy, age-related macular degeneration, ethambutol-induced optic neuropathy, optic neuritis and non-arteritic anterior ischemic optic neuropathy. Though there was a different decrease of CFF in retina and optic nerve diseases, it may be helpful for the differentiation of retinal and optic nerve diseases according to the degree of CFF improvement and the main damaged color light. Moreover, CFF has a good correlation with other visual functions, visual acuity, visual field, and peak time of visual evoked potential. At present, and relevant domestic studies is still in its infancy. This article summarizes the application of CFF in retinal and optic nerve diseases.

糖尿病视网膜病变(diabetic retinopathy,DR)是世界范围内劳动年龄人口视力损伤的主要原因。糖尿病前期和DR临床前期患者作为罹患DR的高危人群，在该阶段可发现视网膜神经元形态功能及视网膜微小血管的改变。视网膜及神经纤维层厚度的变化可部分反映视网膜神经元结构改变；色觉、对比敏感度、视野及视觉电生理等变化可反映视网膜神经元功能改变。随着光学相关断层扫描血管成像技术的发展，临床可以检测出DR之前视网膜微血管的改变。此外，许多生物标志物也可以预测和评估DR。由于目前还没有方法可以阻止DR的发生与进展，临床可以通过观察以上视网膜的改变更为及时地发现DR，以降低其患病率，最大限度地减少DR带来的视力损伤。

Diabetes retinopathy (DR) is the main cause of visual impairment in the working population worldwide. Patients with pre-diabetes and pre-clinic diabetic retinopathy are regarded as in high risk group of DR. The changes in morphology and function of renal neurons and retinal micro-vessels can be found in these patients at this stage. The changes of retinal nerve structure can be partly reflected by changes in the thickness of retina and nerve fiber layer. The changes in function of retinal neurons can be reflected by changes in color vision, contrast sensitivity, visual field and visual electrophysiology.With the development of optical coherence tomography angiography, changes in retinal micro-vessels can be observed prior to clinical detection of DR. In addition, many biomarker can also predict and evaluate DR. Since there is no way to prevent the occurrence and progress of DR at present, more attention should be paid in DR by observing the changes inthe retina mentioned above timely, to reduce its incidence and minimize the visual damage caused by DR.

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.

目的：初步评价折叠顶压球囊(foldable capsule buckle,FCB)治疗孔源性视网膜脱离(rhegmatogenous retinaldetachment,RRD)的有效性、安全性以及手术可操作性。方法：裂孔位置距角膜缘后≥15 mm的采用前瞻性临床病例研究。选择2020年3月至2021年9月在济南明水眼科医院院行FCB植入术治疗裂孔位置距角膜缘后≥15 mm的10例RRD患者(10眼)。应用眼部B型超声、眼底照相评价手术效果。根据术后有无FCB是否暴露、复视情况、排斥反应、眼球运动障碍等术后并发症的发生情况评价手术的疗效和安全性。结果：随访6个月~2年。10例RRD患者在术后通过眼部B超、眼底照相及光学相干断层扫描(opticalcoherence tomography,OCT)评估视网膜均复位。1例合并黄斑区视网膜脱离的患者视力提高。9例患者术后出现复视，术后1~3个月复视消失，1例在术后4个月仍存在复视，行FCB取出，术后视网膜未出现再脱离，复视症状消失。结论：初步研究可确定折叠顶压球囊植入治疗裂孔位置比较靠后(距角膜缘后≥15 mm)且传统巩膜扣带术操作难度大的孔源性视网膜脱离安全、有效，对眼球损伤小，易于操作。

Objective: To preliminarily evaluate the effectiveness, safety and surgical operability of foldable capsule buckle (FCB) in the treatment of rhegmatogenous retinal detachment (RRD). Methods: It is a prospective clinical case study. Ten patients (10 eyes), with a distance of ≥ 15 mm from the posterior margin of the angular membrane at the location of the fissure, who underwent FCB implantation surgery for RRD at Jinan Mingshui Ophthalmology Hospital from March 2020 to September 2021 were enrolled. The surgical outcome was evaluated by B-ultrasound, fundus photography and optical coherence tomography (OCT). The surgical efficay and safety were evaluated by the postoperative complications, such as FCB exposure, diplopia, rejection, and eye movement limitation. Results: The mean follow-up time was 1 year (6 months to 2 years). Retinal reattachment was evaluated by B-ultrasound, fundus photography and OCT after operation in 10 patients. One patient with macular retinal detachment had improved visual acuity. 9 patients developed diplopia after operation, but diplopia disappears 1-3 months after operation. One patient still had diplopia 4 months after operation, and FCB was removed 4 months after operation. No retinal detachment occurred after operation, and the symptoms of diplopia disappeared.Conclusion: It is confirmed by this preliminary research that the implantation of the foldable capsule buckle is safe and effective to treat rhegmatogenous retinal detachment with a relatively posterior position (≥15 mm from the back of the corneal limbus) with little damage to the ocular and easy to operate, compared with the difficulty and complexity in traditional scleral buckling surgery.

视网膜神经纤维层是视网膜的最内层，主要由来自视网膜神经节细胞的无髓鞘轴突组成，此外还有神经胶质细胞与视网膜血管，其厚度与年龄、眼球增长、眼底结构改变等因素相关。光学相干断层扫描可以清晰展示角膜、视网膜、脉络膜、视神经等高分辨率断层图像，可以在活体上显示生物学组织的细微结构，在临床与科研中已获得广泛应用。在青光眼视神经病变中，光学相干断层扫描可以发现视野异常前的视网膜神经纤维层损害，已成为青光眼早期诊断与视神经损伤程度检测的重要手段。除视神经病外，越来越多的研究表明许多视网膜血管疾病、神经元变性疾病等视网膜疾病也有视网膜神经纤维层的损伤。探讨视网膜疾病与神经纤维层的关系，将有利于进一步推进对视网膜疾病发病机制及病理改变的认识。本文就视网膜神经纤维层的定量评估与多种视网膜疾病的关系展开综述，为其在视网膜疾病中的应用提供参考。

The retinal nerve fiber layer, the innermost layer of the retina, consists mainly of unmyelinated axons from retinal ganglion cells, as well as glial cells and retinal blood vessels , the thickness of which is related to factors such as age, ocular growth and fundus structure changes. Optical coherence tomography (OCT) can clearly display the cornea, retina, choroid, optic nerve and other high-resolution tomography images. It can show the fine structure of biological tissues in vivo, which has been widely used in clinical and scientific research. In glaucomatous optic neuropathy, OCT can detect the damage of retinal nerve fiber layer before abnormal visual field, which has become an important means of early diagnosis of glaucoma and detection of the degree of optic ner ve damage. In addition to optic neuropathy, more studies have shown that many retinal diseases such as retinal vascular diseases and neurodegenerative diseases also have retinal nerve fiber layer injury. Exploring the relationship between retinal diseases and nerve fiber layer will be beneficial to further promote the understanding of the pathogenesis and pathological changes of retinal diseases. This paper reviews the relationship between the quantitative evaluation of retinal nerve fiber layer and various retinal diseases, and provides reference for its application in retinal diseases.

玻璃体视网膜疾病并发白内障患者行玻璃体切割术联合超声乳化白内障摘除术，即前后节联合手术，是高效的手术方式，而后囊膜破裂(posterior capsular rupture,PCR)是超声乳化白内障摘除术的术中并发症之一，能够及时、有效地处理PCR，稳定、安全地植入人工晶状体(intraocular lens,IOL)，对于顺利完成后段手术，减少术后并发症十分重要。本文将对前后段联合手术中后囊膜破裂的术中处理、以及IOL光学部夹持固定法植入IOL的手术技术要点进行总结。

Combined surgery of pars plana vitrectomy (PPV) and phacoemulsification is an effective and safe way for management of retinal diseases complicated with cataract. Posterior capsular rupture (PCR) is one of the common intraoperative complications of phacoemulsification, and it is thus very important to deal with it promptly and efficiently, and ensure the subsequent procedures of intraocular lens (IOL) implantation as well as PPV. We will summarize the key points of the surgical technique for management of PCR and capture of IOL optic during combined surgery.

糖尿病视网膜病变是最为常见的糖尿病微血管并发症，主要由糖尿病引起的机体代谢紊乱导致。而然在临床工作中发现，部分患者通过单纯控制血糖以延缓糖尿病视网膜病变进展，所取得效果不甚理想，一些其他因素对于糖尿病视网膜病变的发生、发展，也起到不可忽视的作用。研究表明，在并发高脂血症的糖尿病视网膜病变患者中，胆固醇代谢异常是诱发视网膜病变的主要原因之一。胆固醇代谢异常通过减弱肝脏X受体，导致胆固醇在视网膜上不断积累，降低视网膜血管内皮功能，从而造成视网膜缺血、缺氧环境的形成，又可通过增加炎症因子和细胞黏附分子-1的表达，使原本病态的糖尿病视网膜血管变得更加脆弱，该文总结了糖尿病视网膜病变的病理因素，对比分析当前糖尿病视网膜病变的主要治疗手段，通过分析胆固醇逆向转运(cholesterol reverse transport,RCT)途径转运对糖尿病视网膜病变发生、发展的影响，发现降低高血脂可提高糖尿病视网膜病变的治愈率，这将为糖尿病视网膜病变的临床防治工作提供新思路。

Diabetic retinopathy is the most common diabetic microvascular complication, which is mainly caused by metabolic disorders caused by diabetes. However, in clinical work, it is found that some patients do not achieve satisfactory results in delaying the progress of diabetic retinopathy by simply controlling blood sugar, and some other factors contribute to the occurrence and development of diabetic retinopathy. Also played a role that can not be ignored. Studies have shown that abnormal cholesterol metabolism is one of the main causes of retinopathy in diabetic retinopathy patients with hyperlipidemia. Abnormal cholesterol metabolism leads to the accumulation of cholesterol in the retina and the decrease of retinal vascular endothelial function by weakening the X receptor in the liver, resulting in the formation of retinal ischemia and hypoxia environment. it can also increase the expression of inflammatory cytokines and cell adhesion molecule-1 to make the originally morbid retinal vessels more fragile. This paper summarizes the pathological factors of diabetic retinopathy. By comparing and analyzing the main treatment methods of diabetic retinopathy at present, and by analyzing the influence of cholesterol reverse transport (cholesterolreversetransport,RCT) pathway on the occurrence and development of diabetic retinopathy, it is found that reducing hyperlipidemia can improve the cure rate of diabetic retinopathy, which will provide new ideas for the clinical prevention and treatment of diabetic retinopathy.

近年来，眼部电流刺激(electrical stimulation,ES)在不同方向的研究中逐渐揭示了其在多种视网膜疾病中的潜在治疗价值。其中，经角膜电刺激(transcorneal electrical stimulation,TES)作为一种非侵入性的治疗方法，能对视网膜、视神经、眼底血管及其相关结构产生积极的影响。TES能够改善视力，在保护感光细胞和减缓疾病进展方面显示出积极效果，提高患者的生存质量，还能够在不损伤眼球的情况下调节大脑中的神经元活动，为视网膜疾病的治疗提供一种新的选择。该文对近年来TES在视网膜色素变性(retinitis pigmentosa,RP)、年龄相关性黄斑变性(age-related macular degeneration,AMD)、视网膜血管病、青光眼以及视神经病变等疾病中的应用研究进行了综述。研究发现，TES治疗是一种安全且无需手术的辅助治疗工具，具有广泛的应用前景。该文旨在为临床医师提供一个全面的TES研究概述，并深入探讨其在眼科学领域的潜在应用价值。然而，TES治疗的具体机制仍需进一步探讨，以便更好地应用于临床实践。同时，未来研究还应关注TES与其他治疗方法相结合的效果，以期为患者提供更多有效的治疗选择。

In recent years, electrical stimulation of the eye (ES) has gradually revealed its potential therapeutic value in a variety of retinal diseasesin different directions. Among them, transcorneal electrical stimulation (TES), as a non-invasive treatment, can have a positive effect on the retina, optic nerve, fundus vessels and related structures. TES can improve vision, show positive effects in protecting photoreceptor cells and slowing disease progression, improve the quality of life of patients, and can regulate neuronal activity in the brain without damaging the eyeball, providing a new option for the treatment of retinal diseases. The research on the application on TES on retinitis pigementosa (RP), age-related macular degeneration (AMD), retinal angiopathy, glaucoma and optic neuropathy are reviewed in this article. It is found in the study that TES therapy is a safe and surgery-free adjuvant therapy tool, and has a wide application prospect. The purpose of this article is to provide clinicians with a comprehensive overview of TES research,and to explore its potential application value in the field of ophthalmology. However, the specific mechanism of TES therapy still needs to be further explored in order to better apply in clinical practice. At the same time, future studies should also focus on the effect of combining TES with other treatment methods, in order to provide more effective treatment options for patients.

糖尿病视网膜病变是糖尿病引起的微血管病变之一，是不可逆性致盲的眼病。根据其病程可分为根据其病程可分为非增殖期和增殖期，其中还包括糖尿病性黄斑水肿。全科医师需要检测量裸眼视力、矫正视力和眼压，通过裂隙灯显微镜评估眼前节以及眼底检查来评估眼部整体情况。控制血糖、血压、血脂对改善预后很重要。需要重视餐前、餐后血糖，糖化血红蛋白和代谢记忆，一线降血压药物包括血管紧张素转化酶抑制剂和血管紧张素Ⅱ受体阻断剂，调脂药物首选他汀类，而非诺贝特有额外的视网膜保护作用。干预生活方式，宣教，早期发现也同样重要。全科医师需要进行眼底筛查和评分，及时转诊至眼科治疗。眼科治疗包括全视网膜激光光凝术、经平坦部玻璃体切除术、玻璃体抗血管内皮生长因子药物注射术。

Diabetic retinopathy is one of the microvascular diseases caused by diabetes, it is an irreversible blindness eye disease. According to its course, it can be divided into non-proliferative diabetic retinopathy and proliferative diabetic retinopathy, including diabetic macular edema. Te general practitioner needs to measure the uncorrected visual acuity, corrected visual acuity intraocular pressure, use the slit lamp microscope to exam the anterior segment and fundus to evaluate the overall condition of the eye. Controlling blood glucose, blood pressure and blood lipid is very important to improve the prognosis. Attach importance to pre- and postprandial blood glucose, glycosylated hemoglobin and metabolic memory should be carried out. The first-line antihypertensive drugs are angiotensin converting enzyme inhibitors and angiotensin II receptor blockers. Statins are the first choice for lipid-lowering drugs, fenofibrate has additional protective efect of retinal. Intervention in lifestyle, education and early detection are is important. Te general practitioner needs to perform fundus screening and scoring, timely refer to ophthalmology department for treatment. Ophthalmic treatment includes panretinal laser photocoagulation, pars plana vitrectomy, and intravitreal injection of anti-vascular endothelial growth factor drugs.