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.
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.
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.
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.
慢性中心性浆液性脉络膜视网膜病变(cCSC)以广泛的脉络膜视网膜异常为特征，包括脉络膜血管扩张及其引发的弥漫性视网膜色素上皮病变和浆液性视网膜脱离，常累及黄斑区，引起视功能损害。传统观点认为其可能由急性CSC演变而来，但近期研究显示两者在临床上存在明显差异。其病情反复、迁延，预后较差。随着光学相干断层扫描血管造影(OCTA)、超广角成像和en face重建成像等新多模式影像(MMI)技术的出现和人工智能及机器学习的发展，更多有意义的cCSC影像学特征不断出现。文章详细介绍了cCSC在眼底成像、眼底自发荧光(FAF)、光学相干断层扫描(OCT)、眼底荧光素血管造影(FFA)、吲哚菁绿血管造影和OCTA等影像技术中的表现，并探讨了人工智能在识别CSC分类及其OCT 生物标志物等方面的应用。不同影像技术在cCSC的诊断和研究中各有优势，如FAF可能是评估疾病进展及变化的有效手段，OCT可更直观地观察视网膜结构的改变，FFA是识别渗漏点的重要检查手段，而OCTA可能是评估脉络膜微循环的的最佳手段等。这些MMI研究进展为深入了解cCSC的病理生理机制及临床特征提供了重要线索，有助于提高诊断的准确性和效率，改善患者的预后和生活质量。
Chronic central serous chorioretinopathy (cCSC) is characterized by extensive retinochoroidal abnormalities. This includes difuse retinal pigment epitheliopathy and serous retinal detachment associated with choroidal vasodilatation, ofen involving the macula and cause visual impairment. It was originally considered that it might evolve from acute CSC, but recent studies have shown significant clinical differences between the two. It tends to recur, be prolonged, and have an unfavorable prognosis. With the advent of new multimodal imaging (MMI) techniques such as optical coherence tomography angiography (OCTA), ultra-wide-feld imaging, and en face reconstruction imaging, along with the advancement of artificial intelligence and machine learning, more significant cCSC imaging characteristics have been constantly emerging. Tis article provides a comprehensive overview of cCSC’s imaging features across various modalities, including fundus photography, fundus autofluorescence (FAF), optical coherence tomography (OCT), fuorescein angiography (FFA), indocyanine green angiography, and OCTA. It also explores the application of artifcial intelligence in identifying CSC classifications and OCT biomarkers. Different imaging techniques have their own advantages in the diagnosis and study of cCSC, such as FAF being an efective means to assess disease progression and changes, OCT providing a more intuitive observation of retinal structural changes, FFA being an important tool for identifying leakage points, and OCTA possibly being the best means to assess choroidal microcirculation. Tese MMI research advancements ofer crucial insights for clinicians, aiding in more accurate diagnosis and efective treatment, thereby potentially improving patient outcomes and quality of life.
糖尿病视网膜病变(diabetic retinopathy, DR)作为糖尿病的一种常见并发症是导致工作年龄人群失明的主要原因。血糖变异性(glycemic variability, GV)指血糖波动的程度。最新研究表明，GV与糖尿病患者的代谢状况和微血管病变密切相关。该文综述了GV对DR的影响及其研究进展。GV是指血糖水平在高点和低点之间波动的不稳定状态，分为长期GV和短期GV。长期GV主要通过空腹血糖(fasting plasma glucose, FPG)、餐后血糖(postprandial plasma glucose, PPG)和糖化血红蛋白(glycated hemoglobin, HbA1c)评估，短期GV则通过血糖标准差(standard deviation, SD)、变异系数(coefficient of variation, CV)、低血糖指数(low blood glucose index, LBGI)等指标量化。研究表明，GV是糖尿病大管和微血管并发症的重要风险预测因子，与冠状动脉综合征、心肌梗死、脑卒中、糖尿病肾病、周围神经病变等密切相关。在DR方面，GV可能是其进展的风险因素，高GV会加剧氧化应激、炎症反应、内皮功能障碍和新生血管生成，从而促进DR的发展。治疗策略包括动态血糖监测系统、药物干预(如基础胰岛素、阿格列汀等)、合理饮食和运动等，这些方法可改善GV，降低并发症风险，提高患者预后和生活质量。
Diabetic retinopathy (DR) is a common complication of diabetes and is a leading cause of blindness in the working-age population. Glycemic variability (GV) refers to the degree of fluctuation in blood glucose levels. Recent studies have shown that GV is closely related to the metabolic status and microvascular complications in patients with diabetes. This article reviews the impact of glycemic variability (GV) on diabetic retinopathy (DR) and the latest research progress.GV is defined as the unstable state of blood glucose levels fluctuating between highs and lows, which is categorized into long-term GV and short-term GV. Long-term GV is mainly assessed through fasting plasma glucose (FPG), postprandial plasma glucose (PPG), and glycated hemoglobin (HbA1c). Short-term GV is quantified by indicators such as the standard deviation of blood glucose (SD), coefficient of variation (CV), and low blood glucose index (LBGI).Studies have shown that GV is an important risk predictor for both macrovascular and microvascular complications in diabetic patients, being closely associated with conditions such as coronary artery syndrome, myocardial infarction, stroke, diabetic nephropathy, and peripheral neuropathy. Regarding DR, GV is likely a risk factor for its progression. High GV can exacerbate oxidative stress, inflammatory responses, endothelial dysfunction, and neovascularization, thereby promoting the development of DR.Treatment strategies include continuous glucose monitoring systems, pharmacological interventions (such as basal insulin, alogliptin, etc.), as well as proper diet and exercise. These approaches can improve GV, reduce the risk of complications, and enhance patients' prognosis and quality of life.
3位国际视网膜专家在中山眼科中心(Zhongshan Ophthalmic Center，ZOC)眼底病中心进行临床查房并讨论了4例具有挑战性且不寻常的视网膜病例：1)VHL病合并视网膜血管母细胞瘤的11年 随访观察；2)半剂量光动力疗法(photodynamic therapy，PDT)或微脉冲激光光凝治疗中心性浆液性视网膜病变(central serous chorioretinopathy，CSC)的观察；3)视神经缺陷儿童的诊断与治疗；4)合并虹膜晶状体脉络膜缺损的视网膜脱离(retinal detachment，RD)的治疗选择。通过讨论有助于我们更好地了解这四例视网膜疾病的发病机制和治疗方法，及其与全身疾病的关系。
目的：探讨珠海地区早产儿视网膜病变（retinopathy of prematurity，ROP）的患病情况及临床特点。方法：回顾分析珠海市妇幼保健院2009年5月至2018年12月 5 473 例（10 946 只眼）早产儿的眼病筛查资料。结果：共筛查出 185 例（370 眼）患有不同程度的 ROP，患病率为 3.38%。33 例（66 眼）需要治疗，占 17.84%。低出生体重组出生孕周为 26～31，32～33，34～36的 ROP 患儿分别为 133，13，9 例，ROP 发病率分别为 14.9%，1.4%，1.3%，差异具有统计学意义（P < 0.05）。高出生体重组出生孕周为 26～31，32～33，34～36 的 ROP 患儿分别为 1，5，24例，ROP 发病率分别为 7.1%，1.1%，1.0%，差异无统计学意义（P > 0.05）。33 例严重 ROP 患儿（需要干预治疗的 ROP）中，低出生体重组出生孕周为 26～31，32～33，34～36 的严重ROP患儿分别为 29，3，1 例，发病率分别为 3.2%，3%，0.1%，差异具有统计学意义（P < 0.05）。高出生体重组无严重 ROP 患儿。结论：珠海地区近十年的早产儿 ROP 患病率为 3.38%，出生体重和胎龄是 ROP 发病的危险因素。严重ROP患儿的出生体重均 <2 000 g。
Objective: To investigate the clinical characteristics of retinopathy of prematurity (ROP) in Zhuhai.
Methods: The eye screening data for 5,473 (10,946 eyes) premature infants born from May 2009 to December 2018 in the Maternal and Child Health Hospital of Zhuhai were retrospectively analyzed.Results: In the 5 473 premature babies examination, 185 cases (3.38%) were detected with different degrees of ROP. The number of cases requiring treatment was 33 (17.84%). In the low birth weight group, the ROP patients with 26–31, 32–33, and 34–36 weeks were 133 (14.9%), 13 (1.4%), and 9 (1.3%), respectively; the difference was statistically significant (P < 0.05). In the high birth weight group, the ROP patients with birth weeks of 26–31, 32–33, and 34–36 were 1 (7.1%), 5 (1.1%), and 24 (1.0%), respectively; the difference was not statistically significant (P > 0.05). Among the 33 children with severe ROP (requiring intervention treatment), there were 29 (3.2%), 3 (3%), and 1 (0.1%) with birth weeks of 26–31, 32–33, and 34–36, respectively, in the low birth weight group; the difference was statistically significant (P < 0.05). The severe ROP was 0 in the high birth weight group.Conclusion: The prevalence of ROP in premature infants is 3.38% in the past decade in Zhuhai. Birth weight and gestational age are risk factors for ROP. The birth weight of infants with severe ROP is less than 2 000 g.
目的：检测 2 型糖尿病患者眼房水中血管内皮生长因子（Vascular endothelial growth factor, VEGF）和白细胞介素-6（Interleukin-6, IL-6）的含量，并探讨其临床意义
方法：在白内障手术过程中获取 66 例 2 型糖尿病患者的房水，采用双抗体夹心酶联免疫吸附（ELISA）法测定 VEGF 和 IL-6 的含量。根据手术后散瞳眼底检查和眼底荧光素血管造影检查确定糖尿病视网膜病变的分期。实验组分为：无糖尿病视网膜病变组（NDR）21 例、单纯型糖尿病性视网膜病变组（BDR）26 例、增生型糖尿病性视网膜病变组（PDR）19 例，正常对照组为健康的老年性白内障患者 20 例。
结果：NDR 组、BDR 组、PDR 组的房水 VEGF 含量分别为（240.30 ± 26.15）pg/ml、（292.27 ± 58.91）pg/ml、（477.41 ± 91.01）pg/ml，IL-6 含量分别为（160.83 ± 33.41）pg/ml、（238.60 ± 62.23）pg/ml、（389.13 ± 90.35）pg/ml，对照组房水 VEGF 含量为（140.58 ± 26.27）pg/ml、IL-6 含量为（82.72 ± 21.53）pg/ml，对照组与实验组比较差异均有统计学意义（F = 113.67，P < 0.01；F = 106.53，P < 0.01）。实验组房水中的 VEGF 与 IL-6 含量有相关性（r = 0.995，P < 0.01）；糖尿病患者的病程与房水中 VEGF（r = 0.792，0.826，0.841 均 P < 0.01）、IL-6（r = 0.829，0.817，0.896 均 P < 0.01）含量有相关性。
结论：VEGF、IL-6 在糖尿病视网膜病变的形成过程中有重要作用，且两者之间有相关性。
Purpose: To explore the role of vascular endothelial growth factor (VEGF) and interleukin-6 (IL-6) in the aqueous humor in the pathogenesis of diabetic retinopathy (DR).
Methods: Aqueous humor samples were collected in type 2 diabetic patients during cataract surgery. The classification of DR was assigned based on the fundus examination and fluorescein angiography after cataract surgery. The experiment group included non-diabetic retinopathy (NDR, 21 cases), background diabetic retinopathy (BDR, 26 cases), and proliferative diabetic retinopathy (PDR, 19 cases). The control group was the healthy cataract patients (20 cases). The levels of VEGF and IL-6 in the aqueous humor were assessed using the ELISA technique.
Results: The level of VEGF in NDR, BDR, and PDR cases were (240.30 ± 26.15) pg/ml, (292.27 ± 58.91) pg/ml, and (477.41 ± 91.01) pg/ml, respectively. The level of IL-6 in NDR, BDR, and PDR cases were (160.83 ± 33.41) pg/ml, (238.60 ± 62.23) pg/ml, and (389.13 ± 90.35) pg/ml, respectively. The levels of VEGF and IL-6 in the aqueous humor from the control group were (140.58 ± 26.27) pg/ml, (82.72 ± 21.53) pg/ml. The levels of VEGF and IL-6 were significantly different in experiment and control groups (F = 113.67, P < 0.01; F = 106.53, P < 0.01). In the aqueous humor of diabetic patients increased significantly (P < 0.1). The levels of VEGF and IL-6 were significantly correlated with each other in the experiment group (r = 0.995, P < 0.01). The levels of VEGF (r = 0.792, 0.826, 0.841, P < 0.01) and IL-6 ((r = 0.829, 0.817, 0.896, P < 0.01) were also significantly correlated with the duration of DR.
Conclusion: VEGF and IL-6 play important roles in the development of DR. The levels of these two factors are correlated with each other in DR patients.
