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.
帕金森病(Parkinson’s disease,PD)是老年人常见的神经系统退行性疾病,眼部及视觉功能障碍是PD常见的非运动症状之一,进一步影响其生活质量。已有研究表明PD患者视网膜内存在多巴胺浓度的减少以及α突触核蛋白的沉积。目前,PD仍缺乏有效的早期诊断及病情评估工具,光学相干断层扫描及光学相干断层扫描血管成像技术可以显示视网膜各层微细结构及微血管的异常,应用该技术研究者发现PD患者视乳头旁视网膜神经纤维层及黄斑区视网膜的厚度均存在不同程度的变薄,视网膜浅层及深层毛细血管丛的毛细血管密度和复杂性下降。进一步研究者应用该技术在PD临床应用中进行了探索,并发现其可用于检测早期PD中发生的病理变化,反映疾病的病程及严重程度,并且在鉴别诊断中起到一定的作用。总而言之,视网膜相关检测可能成为评估PD患者脑病理严重程度的指标,并且帮助疾病诊断和监测疾病的进展,不过这仍需要大样本、多中心的重复研究以提供更多理论依据。
Parkinson’s disease is a common neurodegenerative disease in the elderly, and ocular and visual dysfunction is one of the common non-motor symptoms of PD, further affecting PD patients’quality of life. Reduced dopamine concentrations and deposition of α-synuclein in the retina of PD patients have been shown in studies. At present, there is still a lack of effective tools for early diagnosis and assessment of PD. Optical coherence tomography and optical coherence tomography angiography can reveal abnormalities in the microstructure and microvasculature of the retinal layers, and researchers applying these techniques have found that the thickness of the parapapillary retinal nerve fiber layer and the retina in the macula in PD patients have had varying degrees of thinning, and the density and complexity of capillaries in the superficial and deep capillary plexus of the retina have been reduced. Further, investigators have explored the clinical application of these techniques in PD and have found that they can be used to detect pathological changes occurring in early PD, reflect the course and severity of the disease, and play a role in differential diagnosis. In conclusion, retinal-correlated testing may be an indicator to assess the severity of brain pathology in PD patients and to aid in disease diagnosis and monitoring the progression of PD, although large sample, multicenter replication studies are still needed to provide more reliable results.
随着移植技术逐年发展,异基因造血干细胞移植患者的生存期延长,长期并发症成为影响患者预后及生活质量的主要原因。眼移植物抗宿主病是异基因造血干细胞移植术后最常见的眼部并发症,发生率可高达50%以上。根据发病时间可分为急性及慢性眼移植物抗宿主病,临床上最常以慢性炎症及眼表组织纤维化为特点,主要表现为干眼和不同程度的角结膜炎,治疗较为棘手,可不同程度影响患者视觉质量及生活质量,严重可致盲。近年来眼移植物抗宿主病越来越受到国内外学者重视,其发病机制、临床特点、诊断及治疗相关研究逐渐深入,文章针对眼移植物抗宿主病的临床诊疗新进展进行综述。总体而言,眼移植物抗宿主病早期识别仍较为困难,早期诊断策略有待进一步探索。目前治疗对眼移植物抗宿主病的效果较为有限,或缺乏充足的循证医学证据,临床上缺乏针对不同严重程度及疾病活动度的分级诊疗策略,未来有待进一步探索新的治疗靶点及疾病活动监测指标,将有助于改善患者长期预后及生活质量。
Despite advancements in allogeneic hematopoietic stem cell transplantation techniques leading to improved overall survival rates, long-term complications have emerged as the primary contributors to poor prognosis and diminished quality of life. Ocular graft-versus-host disease (oGVHD), a prevalent complication affecting over 50% of patients post-transplantation, frequently manifests as refractory dry eye, often accompanied by keratoconjunctivitis. Patients with oGVHD routinely suffer from visual impairment and a decline in their quality of life.Currently, research into the mechanisms, clinical features, diagnosis, and treatment of oGVHD has progressively deepened. This article reviews the latest advancements in the clinical diagnosis and management of oGVHD. Notably, there is a pressing need for strategies focused on early diagnosis and treatment, as early recognition of oGVHD remains challenging. Existing treatments for oGVHD either exhibit limited efficacy or lack robust clinical evidence to support their use as the best available options.Further research is imperative to develop tiered diagnostic and treatment approaches, including the exploration of novel therapeutic targets and biomarkers for disease detection. Such endeavors hold the promise of enhancing patients' long-term prognosis and quality of life.
谷氨酸是哺乳动物中枢神经系统中的主要兴奋性神经递质,谷氨酸酶系统的持续激活会导致神经元的兴奋性毒性,进而引起神经元损伤和细胞死亡。兴奋性氨基酸转运体家族成员是一种多次跨膜蛋白,位于突触前膜、突触囊泡和神经胶质细胞膜上,也是一种高亲和力的钠钾依赖性载体,能够不断清除细胞外残留的谷氨酸,维持正常的突触内外谷氨酸水平和细胞内氧化还原稳态,对于保护细胞免受兴奋性毒性以及氧化应激损伤至关重要,兴奋性氨基酸转运体家族成员表水平达的失调与多种中枢神经系统疾病神经退行性变的发生和发展密切相关。在视网膜组织中,兴奋性氨基酸转运体家族成员广泛表达。目前大量研究表明,兴奋性氨基酸转运体家族成员广泛参与了青光眼、视网膜缺血再灌注损伤、年龄相关性黄斑变性等眼部疾病的发病,但具体机制有待进一步阐明。为此,文章综述了兴奋性氨基酸转运体家族成员的生理功能及其在相关眼科疾病发生和发展中作用的研究进展,为进一步阐明相关眼病发病的分子机制及新的防治靶点的发现提供新的视角。
SGlutamate is the primary excitatory neurotransmitter in the mammalian central nervous system. Persistent activation of the glutamatergic system can lead to excitotoxicity, resulting in neuronal damage and cell death. Members of the excitatory amino acid transporter (EAAT) family are multi-transmembrane proteins located on the presynaptic membrane, synaptic vesicles, and glial cell membranes. They function as high-affinity, sodium-potassium-dependent transporters, continuously clearing extracellular residual glutamate to maintain normal intra- and extracellular glutamate levels and intracellular redox homeostasis. This process is crucial for protecting cells from excitotoxicity and oxidative stress-induced damage. Dysregulation of EAATs is closely associated with the onset and progression of neurodegenerative diseases in the central nervous system. EAAT family members are widely expressed in retina. Numerous studies have demonstrated that these transporters are extensively involved in the pathogenesis of ocular diseases, including glaucoma, retinal ischemia-reperfusion injury, and age-related macular degeneration, although the specific mechanisms remain to be elucidated. Therefore, this article reviews the physiological functions of EAAT family members and their role in the development and progression of related ophthalmic diseases, providing new perspectives for further understanding the molecular mechanisms underlying these conditions and identifying novel therapeutic targets.
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.
目的:了解干眼患者自我护理能力水平并分析其影响因素。方法:选取2022年2月—6月在中山大学中山眼科中心就诊的干眼患者为研究对象,采用一般资料调查表、自我护理能力量表、一般自我效能感量表对患者进行调查分析。结果:共调查293例干眼患者,其自我护理能力评分为(113.34±9.98)分,处于中等水平。相关性分析中干眼患者的自我护理能力总分与自我效能感得分呈正相关(r=0.421,P<0.001),多重线性回归分析显示,累计屏幕使用时间>10 h/d、合并全身疾病、低自我效能感评分是干眼患者自我护理能力的危险因素(P<0.05)。结论:干眼患者自我护理能力水平处于中水平,仍需加强。医护工作者在工作中应重点关注屏幕使用时间长、合并全身疾病及自我效能感低的患者,并制定相应的护理对策,以改善患者的自我护理能力水平。
Objective: To understand the self-care ability of patients with dry eye and analyze its infuencing factors. Methods: A total of 293 patients with dry eye were selected from Zhongshan Ophthalmic Center, Sun Yat-sen University from February 2022 to June 2022, the general data Questionnaire the general self-efcacy scale, and the self-care ability scale survey were collected. Results: A total of 293 patients with dry eye were surveyed, and the self-care ability score was 113.34±9.98, which was at the medium level. The total score of self-care ability, the scores of self-concept, self-care responsibility, health knowledge level and self-care skills of patients with dry eye were positively correlated with the scores of self-efcacy (r=0.421, all P<0.001).Multiple linear regression analysis showed that cumulative screen usage time>10 hours/day, comorbid systemic diseases, and low self-efficacy scores were risk factors for self-care ability in patients with dry eye (P<0.05). Conclusions: Te self-care ability of patients with dry eye disease is at a medium level, and still needs to be strengthened. Medical workers should focus on patients with prolonged screen usage, comorbid systemic diseases, and low self-efficacy in their work, and tailor relevant nursing strategies to improve their self-care abilities.
目的:利用信息化手段,优化眼遗传病患者的随访途径,降低病历资料缺失率,助力临床检验科室高效运营。方法:通过态势分析法搜集需求,基于微信公众号平台“中山大学眼科医院小儿遗传”,搭建眼遗传病信息管理系统。根据是否使用眼遗传病信息管理系统、是否受到人员流动限制,将2017年7月1日—2023年11月30日来院进行基因检测的患者分为四组:传统组、传统+人流限制组、微信组和微信+人流限制组,通过χ2检验对眼遗传病信息管理系统进行性能评价。结果:源软件架设在阿里云电子政务平台的眼遗传病信息管理系统,通过加密通讯与医院网络交互。系统主要分为基因检测业务、数据管理和系统管理三大模块。使用该系统的患者或亲属可以在任意时间和地点,自主上传病历资料、签署知情同意书、查询基因检测报告,如有需要还能进行一对一的沟通实现长期随访。在此过程中,患者的临床信息实现数字化。研究共纳入10 662例患者对该系统进行性能评价,使用眼遗传病信息管理系统后,患者病历资料缺失率显著降低,由12.2%(传统+人流限制组)降至2.7%(微信+人流限制组);患者二次来访率由最高的70%(传统组)降至最低的11.7%(微信组);两类比较差异有统计学意义(P<0.001)。结论:眼遗传病信息管理系统的使用显著降低患者病历资料缺失率和眼遗传病患者的二次来访率。
Objective: To optimize the follow-up approach for patients with ophthalmic genetic diseases through informational technology, reduce the loss rate of cases, and facilitate the efficient operation of the clinical laboratory. Methods: Using the SWOT analysis method to collect requirements, ‘Pediatric Genetics of Zhongshan Ophthalmic Center’, an ophthalmic genetics information management system for ophthalmic genetic diseases was established on the Wechat public platform. Based on whether the ophthalmic genetic disease information management system was used and there were personnel mobility restrictions, patients who underwent genetic testing in the hospital for genetic testing from July 1, 2017, to November 30, 2023, were divided into four groups: traditional group, traditional+ lockdown group, Wechat+ lockdown group, and Wechat group. Te chi-square test was used to evaluate the performance of the ophthalmic genetic information management system. Results:The ophthalmic genetic disease information management system, which is based on open-source sofware and hosted on the Alibaba Cloud e-government platform, interacts with the hospital network through encrypted communication. Te system was divided into three modules: gene detection business, data management, and system management. By the system, patients or relatives can upload medical records, sign informed consent, inquire about genetic test reports at any time and anywhere, and conduct one-on-one communication to achieve long-term follow-up if necessary. In this process, the patient's clinical information was digitized. A total of 10,662 patients were included in the study to evaluate the performance of the system. The loss rate of cases was decreased from 12.2%to 2.7%, and the rate of second visits was reduced from 70% to 11.7%, which were statistically different, respectively (P< 0.001). Conclusion: Te application of the ophthalmic genetic information management system has signifcantly reduced the loss rate of cases and the rate of second visits in patients with ophthalmic genetic diseases.
哺乳动物雷帕霉素靶蛋白(mammalian target of rapamycin,mTOR)是一种蛋白激酶,在体内主要参与营养水平、生长代谢的调节。mTOR是癌症、衰老和其他代谢相关病理性疾病的重要靶点,参与了增殖、转分化、自噬等多种生物学过程。眼被认为是具有免疫特权的区域,由于血管系统会影响视力,眼的血管系统位于中心光路以外。眼的许多区域都有将免疫细胞运输至发育不良、受损或衰老有关的病变部位的机制。尽管免疫应答主要是为了修复或保护自身,但是免疫细胞可能会分泌一些细胞因子,导致炎症或纤维化,进而损害视力。研究证实,mTOR与翼状胬肉、年龄相关性黄斑变性(age-related macular degeneration,AMD)、青光眼、白内障、糖尿病视网膜病变(diabetic retinopathy,DR)、眼部肿瘤等多种眼病密切相关。目前,mTOR抑制剂通常被用作免疫抑制剂,用于癌症的治疗,但mTOR抑制剂用于眼部疾病的报道尚少。因此,该文就mTOR信号通路在相关眼科疾病中的作用、调控机制、药物治疗等方面进行简要综述,为相关眼科疾病的病理机制与治疗提供思路,以便后续开展更深入的研究。
Mammalian target protein of rapamycin (mTOR) is a protein kinase that primarily involves in the regulation of nutrient levels andgrowth metabolism in vivo. mTOR serves as a crucial target for cancer, aging, and other metabolic related pathological diseases, participating in various biological processes such as proliferation, transdifferentiation, and autophagy. Te eye is considered an area with immune privilege, as the vascular system afects vision and is located outside the central light path. Many areas of the eye have mechanisms for transporting immune cells to the afected areas related to developmental, damaged, or aging. Although the immune response is primarily aimed at reparing or protecting itself, immune cells may secrete some cytokines, leading to infammation or fbrosis, which in turn can damage vision. Results from studies have confirmed that mTOR is closely related to pterygium, age-related macular degeneration (AMD), glaucoma, cataract, diabetic retinopathy (DR), eye tumors and other eye diseases. Currently, mTOR inhibitors are widely used as immunosuppressants and approved for cancer treatment; however, there are few reports on the use of mTOR inhibitors for eye diseases. Therefore, in the article it provides a brief overview of the role, regulatory mechanisms, and drug treatment of the mTOR signaling pathway in related ophthalmic diseases, providing ideas for the pathological mechanisms and treatment of related ophthalmic diseases, in order to carry out more in-depth research in the future.
目的:旨在研究按移植指征分类以及移植前角膜血管形成对手术后5年内排斥反应和移植物失败率的相对风险。方法:分析1999—2017年间,英国移植登记处记录的所有因圆锥角膜(keratoconus,KC)、人工晶状体大泡性角膜病(pseudophakic bullous keratopathy,PBK)或既往感染(病毒/细菌/真菌/原生动物)而首次进行角膜移植的成年人。统计移植前受体角膜血管化象限的数量、血管化类型、移植后排斥反应的间隔时间(如果有的话)以及移植后5年的结果。通过多变量风险调整Cox回归法进行排斥反应和移植失败的危险因素建模。结果:KC、PBK和感染患者的角膜血管形成率分别为10%、25%和67%。只有当存在浅表和(或)深部血管形成时(HR分别为1.3和1.4,P=0.004),存在两个以上象限的血管形成时,PBK患者移植排斥反应的风险才会增加(HR=1.5,P=0.0004)。因既往感染而接受移植的个体在四个象限的血管形成中发生排斥反应的风险增加(HR=1.6,P=0.003)。在任何一组中,经过风险调整后,与血管形成有关的移植失败率并未上升。对于含有血管的受体角膜,相对于穿透性KC和PBK移植,没有充分的证据显示板层移植在降低排斥反应或失败风险方面存在优势。结论:血管化是5年内角膜移植排斥反应的危险因素。移植的适应证对这种风险的具有临床意义。
Objective: To investigate the relative risk of pretransplant corneal vascularisation on rate of rejection and graft failure within 5 years of surgery when categorised by indication for transplantation. Methods: We analysed all adults recorded in the UK transplant registry who had a first cornea transplant for keratoconus (KC), pseudophakic bullous keratopathy (PBK) or previous infection (viral/bacterial/fungal/protozoan) between 1999 and 2017. We analysed the number of quadrants of the recipient cornea vascularised before transplant and type of vascularisation, the interval posttransplant to rejection, if any, and the outcome at 5 years post-transplant. Risk factors for rejection and transplant failure were modelled by multivariable risk-adjusted Cox regression. Results: Corneal vascularisation was recorded in 10%, 25% and 67% of patients with KC, PBK and infection, respectively. Individuals with PBK had an increased hazard of transplant rejection only when there were more than two quadrants of vascularisation (HR 1.5, p=0.004) when either superficial and/or deep vascularisation was present (HR 1.3 and 1.4, respectively, p=0.004). Individuals who had a transplant for previous infection had an increased hazard of rejection with four quadrants of vascularisation (HR 1.6, p=0.003). There was no risk-adjusted increase in transplant failure associated with vascularisation in any group. There was weak evidence of reduction in risk of rejection and/or failure associated with lamellar compared with penetrating transplantation in KC and PBK in vascularised recipient corneas. Conclusion: Vascularisation is a risk factor for corneal allograft rejection within 5 years. The indication for transplantation has a clinically significant effect on the magnitude of this risk.
原发性干燥综合征(primary Sj?gren’s syndrome,SS)是一种主要累及外分泌腺体的自身免疫性疾病,患者通常因为严重的干眼症状首先就诊于眼科,大多数临床医师对原发性干燥综合征相关性干眼(Sj?gren’s syndrome dry eye disease,SS-DED)认识不足,可能导致漏诊和误诊。侵入性极小的客观检查及生物标志物的发展,将有助于发现SS-DED的真面目,并可能从新的角度阐释其发病机制,为其诊断、分类及治疗提供新的思路。SS-DED的治疗没有特效的药物,大多数患者需接受多种方法的治疗,以了解哪些方法最有效。
Primary Sj?gren’s syndrome is an autoimmune disease that mainly affects exocrine glands. Patients usually refer to ophthalmologists because of severe dry eye symptoms. Most clinicians have insufficient knowledge with dry eye disease associated with primary Sj?gren’s syndrome probably leading to misdiagnosis or missing the diagnosis.The diagnosis of Sj?gren’s syndrome dry eye disease (SS-DED) is difficult, but the extremely invasive objective examination and the development of biomarkers will help to understand this disease and explain its pathogenesis from a new perspective. There is no specific treatment for the SS-DED, and most patients should receive multiple treatments to select the optimal treatment.