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.
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.
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.
铁死亡是一种以铁沉积和脂质过氧化为主要特征的新型细胞死亡方式，目前在眼科方面的研究不断深入。视网膜因其本身功能和结构特点，易受到氧化应激的影响，而铁死亡已被证明在年龄相关性黄斑变性、青光眼、糖尿病性视网膜病变、视网膜色素变性等视网膜退行性疾病进程中发挥了重要作用。铁代谢途径作为铁死亡的主要调控方式之一，可通过调控细胞内铁稳态，介导芬顿反应形成脂质过氧化物，从而调控细胞铁死亡。转铁蛋白(transferrin,TF)、二价金属转运蛋白1(divalent metal transporter 1,DMT1)、铁蛋白(ferritin,FT)、铁转运蛋白1(ferroportin 1,FPN1)等铁代谢途径关键蛋白涉及细胞内铁离子的摄入、利用、储存、输出等多个方面，对细胞内铁稳态具有重要影响。通过调控铁代谢途径关键蛋白减少铁沉积而抑制铁死亡，可能成为延缓和治疗视网膜退行性疾病的新途径。文章对铁死亡概念、视网膜与铁死亡、铁死亡调控途径、铁代谢途径关键蛋白与视网膜退行性疾病的研究进展进行综述。
Ferroptosis, a novel form of cell death primarily characterized by iron deposition and lipid peroxidation, has been increasingly studied in the feld of ophthalmology. Te retina, due to its specifc functions and structure, is susceptible to oxidative stress. Ferroptosis has been proven to play a crucial role in the progression of retinal degenerative diseases such as age-related macular degeneration, glaucoma, diabetic retinopathy, and retinitis pigmentosa. Te iron metabolism pathway is one of the main regulatory mechanisms of ferroptosis, regulating intracellular iron homeostasis and mediating the formation of lipid peroxides through the Fenton reaction, thereby controlling cellular ferroptosis. Iron metabolism pathways, as one of the main regulatory mechanisms of ferroptosis, can regulate intracellular iron homeostasis and mediate the formation of lipid peroxides through the Fento reaction, thereby controlling cellur ferroptosis. Key proteins involved in iron metabolism pathways, including transferrin (TF), divalent metal transporter 1 (DMT1), ferritin (FT), and ferroportin 1 (FPN1), act as important roles in various aspects such as intracellular iron intake, utilization, storage, and export, exerting signifcant impacts on intracellular iron homeostasis. Regulating key proteins in iron metabolism pathways to reduce iron deposition and inhibiting ferroptosis may emerge aas a novel approach for delaying and treating retinal degenerative diseases. Tis article provides a comprehensive review of the concept of ferroptosis, the relationship between the retina and ferroptosis, the regulatory mechanisms of ferroptosis, and the research progress on key proteins in iron metabolism pathways and retinal degenerative diseases.
年龄相关性黄斑变性(age-related macular degeneration,AMD)是一种发生在黄斑区的退行性变，其中湿性年龄相关性黄斑变性(wet age-related macular degeneration,wAMD)以黄斑区新生血管为主要病理特征，是导致老年人视力受损甚至失明的重要原因，视网膜下纤维化是wAMD最常见的自然后遗症，可导致光感受器、视网膜色素上皮(retinal pigment epithelial,RPE)和脉络膜毛细血管受损，导致不可逆转的中心视力丧失。多种基线特征被发现是视网膜下纤维化的危险因素，可用于预测早期视网膜下纤维化的发生。迄今为止，还没有有效的抗纤维化治疗方法，抗血管内皮生长因子(anti-vascular endothelia growth factor, anti-VEGF)治疗是wAMD的一线治疗方案，该治疗方法不能改善视网膜下纤维化，但及时启动治疗可能有助于预防或延缓纤维化的进展，目前多种靶向分子药物正被研发用于抗纤维化的治疗。该文综述了wAMD视网膜下纤维化的临床表现及意义、预测纤维化形成的基线特征、基本发病机制及潜在的抗纤维化治疗方法，旨在为临床诊治工作提供参考。
Age-related macular degeneration (AMD) is a degenerative disease of the macular, and wet age-related macular degeneration(wAMD) is mainly characterized by macular neovascularization, which is an important reason of visual impairment or even blindness in the elderly. Subretinal fibrosis is the most common natural sequelae of wAMD, which can lead to irreversible central vision loss by damaging photoreceptors, RPE, and choroidal capillaries. Multiple baseline features have been identified as the risk factors for subretinal fibrosis, which can be used to predict the early subretinal fibrosis. Heretofore, no anti fibrotic treatment method is effective. Anti vascular endothelial growth factor (anti VEGF) treatment is the first-line treatment for wAMD. This therapy cannot improve subretinal fibrosis, but timely initiation of treatment may help prevent or delay the progression of fibrosis. Currently, multiple targeted molecular drugs are being developed for anti fibrotic treatment. This article reviews the clinical manifestations and significance of subretinal fibrosis in wet age-related macular degeneration, baseline features for predicting the formation of fibrosis, basic pathogenesis, and potential anti-fibrosis treatment methods,aiming to provide reference for clinical diagnosis and treatment.
孔源性视网膜脱离(rhegmatogenous retinal detachment,RRD)是一种严重威胁视力的眼部疾病，目前治疗手段以手术为主，手术方式主要有视网膜气体填充术(pneumatic retinopexy,PR)、巩膜扣带术(scleral buckling,SB)以及经睫状体扁平部玻璃体切割术(pars plana vitrectomy,PPV)。目前对于RRD手术术式的选择仍然存在争议，因此研究及制定RRD手术方式抉择的临床策略具有重要的临床意义。而临床上制定RRD患者手术方案往往与患者的年龄、视网膜脱离时间、裂孔的类型、位置、数量、大小等等临床因素有关，该文就影响孔源性视网膜脱离手术抉择的相关临床因素进行综述。
Rhegmatogenous retinal detachment (RRD) is a serious eye disease threatening vision. Surgery is main treatment currently, and surgery approaches include pneumatic retinopexy (PR), scleral buckling (SB), and pars plana vitrectomy(PPV). There is still controversy over the selection of RRD surgery approaches, so it is great significant to study and develop clinical strategies for RRD surgery approaches. The surgical plans for RRD patients are often related to clinical factors, such as the patient’s age, retinal detachment time, type, location, quantity, size, etc. This article reviews the related clinical factors affecting the surgical decision for rhegmatogenous retinal detachment.
结节性硬化症(tuberous sclerosis complex，TSC)是一种累及多系统的常染色体显性遗传病，早期呈单一表现，容易漏诊、误诊，以眼部症状为首发特征的新生儿期病例少有报道。本文报告1例早产男婴，出生后1 d眼底筛查发现右眼视网膜散在多个灰白色半透明隆起灶及脱色素斑，回溯胎儿期超声心动图异常高度怀疑TSC，进一步行头颅MRI检查及家族基因检测，在新生儿期明确了这一诊断。
Tuberous sclerosis complex is a multisystemic disease with an autosomal dominant inheritance pattern. Missed diagnosis and misdiagnosis are common for patients with single manifestation in the early stage. There are few documented neonatal cases with ocular symptoms as primary presentation. Here we report a newborn boy presented with retinal hamartoma, retinal achromic patch, fetal cardiac rhabdomyoma and subependymal nodules.Subsequent genetic tests confirm a diagnosis of TSC.
目的：玻璃膜疣主要成分胆固醇对人视网膜色素上皮细胞ARPE-19中细胞膜钙ATP酶1(plasma membrane Ca2+ ATPase 1，PMCA1)、L型电压依赖性钙离子通道(L-type voltage-dependent calcium channel，LVDCC)和细胞膜钠钙交换蛋白1(sodium calcium exchange protein 1，NCX1)表达的影响。方法：体外培养ARPE-19细胞，将细胞分为对照组和胆固醇处理组(2.5 mg/mL)，取样时间为0、6、12、24、48、72 h。通过实时定量PCR检测PMCA1、LVDCC和NCX1 mRNA的表达水平，用蛋白质印迹法检测蛋白质的表达水平。结果：主要负责细胞内钙离子外排的PMCA1的mRNA和蛋白表达水平在胆固醇处理下出现下调。在胆固醇处理下，钙流入通道LVDCC和钙稳态调控蛋白NCX1的mRNA和蛋白表达明显增多，并且呈现时间依赖性，都是在24 h或48 h表达最多后出现回落。其中LVDCC表达上调倍数较大。结论：玻璃膜疣主要成分胆固醇可以影响人视网膜色素上皮细胞中钙转运通道蛋白的表达，PMCA1的表达受到胆固醇抑制， LVDCC和NCX1的表达受到胆固醇处理上调。这可能会影响细胞内钙离子外排，引起钙离子内流，是否能进一步导致细胞内钙超载而引起细胞凋亡，值得探讨。
Objective: To study the effects of cholesterol, the main component of drusen, on the expression plasma membrane Ca2+ ATPase 1 (PMCA1), L-type voltage-dependent calcium channel (LVDCC) and cell membrane sodium calcium exchange protein 1 (NCX1) of ARPE-19 cells. Methods: The ARPE-19 cell line was cultured in vitro, and the cells were divided into a control group and a cholesterol treatment group (2.5 mg/mL). The treatment time was 0, 6, 12, 24, 48, 72 hours. Real-time quantitative PCR was used to detect the expression of PMCA1, LVDCC and NCX1 at the mRNA level, and western blot was used to detect the expression at the protein level. Results: The mRNA and protein expression levels of PMCA1 which mainly responsible for the efflux of intracellular calcium ions, was down regulated under cholesterol treatment. Meanwhile, the expression of the mRNA and protein of the calcium inflow channel LVDCC and calcium stability regulatory protein NCX1 were significantly increased, and the time-dependency was present, which was up expressed to 24 or 48 h and then fell back. Among them, the LVDCC expression had a large number of times. Conclusion: Cholesterol, the main component of drusen, can affect the expression of calcium channels in human retinal pigment epithelial cells. The expression of PMCA1 was suppressed by cholesterol, and expression of LVDCC and NCX1 were up-regulated with cholesterol treatment, which may affect intracellular calcium efflux then cause calcium influx. Whether it can further cause intracellular calcium overload and cell death is worth exploring.
