糖尿病视网膜病变的治疗进展

针对糖尿病视网膜病变（diabetic retinopathy,DR）的不同的阶段,我们可以采取多种方式对疾病进行治疗和控制。DR早期的治疗主要为控制血糖、血压以及血脂,并在此基础上应用适当的药物治疗。而当DR进入中后期时则主要依靠激光治疗和玻璃体手术。新的药物如曲安奈德的应用为治疗中晚期DR提供了新的手段,药物性玻璃体切割为预防和减少玻璃体视网膜黏连、减轻新生血管的生成提供了新方法,也为玻璃体手术中完全清除玻璃体后皮质提供了帮助。本文就DR的治疗进展作一综述。     

糖尿病视网膜病变发生发展的全身及眼局部相关因素

糖尿病性视网膜病变(diabetic retinopathy,DR)是最为常见的致盲性眼底病变之一,其发病机制不明。长期以来,早期对于糖尿病性视网膜病变的治疗只是单纯控制血糖,但这并不能完全阻止糖尿病性视网膜病变的进一步发展。因此,研究全身及眼局部相关因素的影响作用十分重要。近年来,国内外大量研究认为,许多全身及眼局部因素对糖尿病性视网膜病变发生发展起重要作用。本文综述此方面成果,为最终通过全身及眼局部的综合干预为早期防治糖尿病性视网膜病变提供思路。     

糖尿病视网膜病变的诊断和治疗:2016-2018年最新研究进展

糖尿病视网膜病变（diabetic retinopathy,DR）是糖尿病的一种威胁视力的并发症,是致盲的主要原因。DR发病机制复杂,目前尚不明确。大量的证据使人们意识到DR不仅是一种血管疾病,而且是一种神经退行性疾病。目前针对DR治疗方案效果有限,DR的早期诊断、防治至关重要。本文就近两年DR的诊断、治疗的最新研究进展及新的治疗靶点进行综述。     

糖尿病视网膜病变早期优化代谢治疗研究进展

糖尿病视网膜病变（DR）是导致糖尿病人群视力严重损害的主要原因。现有的治疗措施大多针对已有视力受损的中晚期患者,且为有创性治疗,效果有限。因此,迫切需要早期预防DR发生风险或延缓DR进展的非侵入性新疗法和新靶点。早期优化代谢治疗,即在糖尿病早期严格控制血糖、血压、血脂至正常范围,可能预防或改善潜在的、可逆的微血管病变,...     

Mechanism of diabetes-induced microvascular damage and therapeutic potential of ROCK inhibition

The rapid increase in diabetic retinopathy (DR), a common ocular complication of diabetes mellitus, necessitates the development of new therapeutic strategies for the amelioration and treatment of DR, especially in the earlier stages. In the present study, involvement of the Rho/Rho-kinase (ROCK) pathway in diabetic microvasculopathy and the therapeutic potential of fasudil, a selective ROCK inhibitor, were investigated. Retinal microvascular damage secondary to increased leukocyte adhesion substantially contributes to DR in its early stages. Significant Rho/ ROCK activation was observed in the retinal microvasculature of diabetic rats. The ROCK inhibitor, fasudil, protects the vascular endothelium by inhibit- ing leukocyte adhesion and reducing leukocyte-induced endothelial injury mediated through the restoration of endothelial nitric oxide synthase activity, in the retinas of diabetic rats. In co-culture assay of DR leukocytes and microvascular endothelial cells, we investigated the protective mechanisms of fasudil on endothelial damage using L-NAME, an inhibitor of nitric oxide synthase. Leukocytes from DR patients caused endothelial apoptosis via Fas/ FasL interaction, which was significantly reduced by a ROCK inhibition dependent on nitric oxide. The Rho/ROCK pathway plays a critical role in diabetic retinal microvasculopathy and ROCK inhibition may become a new strategy in the amelioration and treatment of DR, especially in its early stages.     

单核细胞趋化蛋白-1在糖尿病视网膜病变中的作用研究进展

糖尿病视网膜病变（DR）是糖尿病最为常见和严重的并发症之一,是成年人视力丧失的主要原因。越来越多的证据表明,炎症在DR的发病机制中发挥关键作用,抗炎治疗或许能有效延缓DR的发生和发展。单核细胞趋化蛋白-1 （MCP-1）作为炎症反应过程中一种重要的趋化因子,通过趋化和激活因子、破坏血视网膜屏障、引起视网膜血管病变、激活...     

中药单体干预糖尿病视网膜神经退行性变的研究进展

糖尿病视网膜病变(DR)传统意义上被认为是视网膜的单纯微血管疾病,目前主流疗法仍然只关注其晚期血管病变并发症和单一分子靶点-血管内皮生长因子(VEGF)。然而现在研究正转向一个更全面的观点,即DR是神经血管单元(NVU)损伤引起的一类神经血管性疾病。在DR早期阶段,糖尿病视网膜神经退行性变(DRN)占主导地位,可能先于微血管异常发生,且神经元细胞的凋亡可进一步导致微血管损伤和血-视网膜屏障(BRB)破坏。因此在早期DR中开发新的治疗策略来预防或逆转DRN是有意义的,然而目前尚没有针对DRN的药物被批准用于临床。近年来研究中药对视网膜保护作用已成为热点,且主要研究集中在中药单体。本文综述了具有代表性的中药单体在DRN中的研究现状,以期为DR的早期治疗与新药研发提供参考。     

糖尿病视网膜病变的早期防治

糖尿病视网膜病变（diabetic retinopathy,DR）是一种难于逆转的致盲性眼病。鉴于目前我国治疗严重、复杂DR的医疗资源非常有限,因此,有必要将防盲工作的重点转移到DR的早期防治方面。但由于我国DR防治体系相对薄弱,尚缺乏根据循证医学原则所制定的恰当的防治指南,故广泛开展DR的早期防治工作尚面临较多困难。为此,充分认识DR早期防治的必要性和重要性,积极推广DR国际分型标准,采用公共卫生的途径,从初级卫生保健抓起,多方通力协作,加强其早期防治的实践和研究工作,将成为各级政府和DR防治工作者所面临的一项重要任务。（中华眼科杂志,2008,44：9-11）     

Systemic considerations in the management of diabetic retinopathy.

PURPOSE: To highlight the systemic factors which affect onset and/or progression of diabetic retinopathy (DR) and to emphasize the role and responsibilities of ophthalmologists and other eye care providers to ensure that appropriate systemic medical evaluation of the patient with diabetes is being pursued. DESIGN: Literature review of publications relevant to diabetic retinopathy, blood glucose control, diabetes mellitus type, hypertension, renal disease, elevated serum lipids, exercise, pregnancy, anticoagulation, thrombolysis, smoking, anemia and antioxidant ingestion. FINDINGS: Intensive blood glucose control and control of systemic hypertension reduce the risk of new onset DR and slow the progression of existing DR. Severe DR may be an indicator of renal disease while severe renal disease and its treatment can affect the progression of DR. Elevated serum lipids are associated with macular exudate and moderate visual loss. Certain types of excessive exercise in patients with advanced stages of retinopathy may aggravate vitreous hemorrhage. During pregnancy, DR should be monitored closely as transient progression of DR can occur. Therapeutic anticoagulation and thrombolysis are not contraindicated at any stage of DR. Anemia can result in progression of DR, smoking in general should be discouraged, and the role of antioxidant therapy requires further study. CONCLUSIONS: Blindness from diabetic retinopathy is now largely preventable with timely detection and appropriate interventional therapy. Routine, repetitive, lifelong, expert clinical retinal examination is essential for the fundamental ophthalmic care of the patient with diabetes. However, diabetes mellitus is a systemic disease and thus optimal ophthalmic care must include diligent evaluation and treatment of concomitant systemic disorders that influence the development, progression and ultimate outcome of diabetic retinopathy. Optimization of these systemic considerations through an intensive, multi-disciplinary, healthcare team-based approach will maximize the ophthalmic and general health of these patients. Ophthalmologists and other eye care providers are critical members of this team with unique responsibilities to ensure that appropriate systemic medical evaluation is being pursued.     

糖尿病视网膜病变相关基因多态性的研究进展

糖尿病视网膜病变（DR）是糖尿病最常见、最严重的并发症之一,发病率和致盲率逐年上升。通常认为其发生、发展与血糖控制情况、糖尿病病程长短等因素有关,而发病机制尚未完全明了。现在越来越多的证据表明其与遗传易感性不同有关。DR是一种多基因作用的疾病,近年来的研究已筛选出数十种可能与之相关的基因多态性,其中包括广受关注的血管内皮生长因子基因多态性、一氧化氮合酶基因多态性等。研究它们在DR发生发展过程中的作用机制,对今后DR风险预测、早期诊断及指导治疗具有重要意义。本文将对DR相关基因多态性的研究进展进行综述。     

Potential therapeutic effects of pigment epithelium-derived factor for treatment of diabetic retinopathy

Diabetic retinopathy (DR), a major micro-vascular complication of diabetes, has emerged as a leading cause of visual impairment and blindness among working adults in the worldwide. The pathobiology of DR involves multiple molecular pathways and is characterized chronic neurovascular degeneration. Current approaches to prevent or to treat DR are still far from satisfactory. Therefore, it is important to develop new therapeutic strategies for the prevention and treatment to DR. Pigment epithelium-derived factor (PEDF), a 50-kDa secreted glycoprotein, has been described as a multi-functional protein. Some emerging evidences indicate that PEDF are able to target multiple pathways exerting neurotropic, neuroprotective, anti-angiogenic, antivasopermeability, anti-inflammation, anti-thrombogenic and anti-oxidative effects in DR. In this review, we addressed the functions of PEDF in different pathways, which could lead to potential therapeutics on the treatment to DR.     

Early detection of diabetic retinopathy

Diabetic retinopathy (DR) is a primary cause of visual impairment worldwide. Diabetes mellitus may be associated with ophthalmoscopically nonvisible neurovascular damage that progresses before the first clinical signs of DR appear. Reduction of the inner neuroretinal layer thickness on macular optical coherence tomography, reduced contrast sensitivity primarily at low spatial frequencies, abnormal results in color vision and microperimetry tests, and a prolonged implicit time recorded by multifocal electroretinography have been proposed for detection of early functional and nonvisible structural neuroretinal changes. Vascular abnormalities such as changes in the retinal vessel caliber, architectural indices, and blood flow have been investigated to evaluate the early stages of DR. The results of optical coherence tomography angiography, retinal vessel oxygen saturation patterns, and elevated levels of circulating blood markers and cytokines have been suggested as early signs of DR. Light-based molecular imaging in rodents has been developed to demonstrate changes in protein expressions in the retinal microvessels as diagnostic biomarkers. Future clinical studies will examine the safety and efficacy of this approach in humans. We summarize all the studies related to subclinical DR biomarkers.     

从视网膜氧化应激与微血管改变谈糖尿病视网膜病变的发病机制和防治策略

糖尿病视网膜病变（DR）是糖尿病患者因长期高血糖而并发的视网膜微循环障碍性眼病，随病情进展可致严重视力损害。DR作为一种病因复杂的多因素疾病，尽管发病机制尚未完全阐明，但氧化应激已被证明是其中一个关键因素。高血糖引起机体多种代谢异常相互作用，诱导视网膜活性氧过度产生、氧化应激损伤增加，导致视网膜线粒体功能障碍、微血管功能障碍、血-视网膜屏障破坏、新生血管形成等一系列病理反应，显著影响DR发生发展的各个阶段。深入研究视网膜氧化应激与微血管改变在DR发病机制中的作用将有助于为防治DR提供新的思路。     

糖尿病视网膜病变易感性与相关基因多态性研究进展

糖尿病视网膜病变(DR)是一种多因素介导的疾病,目前公认DR是由慢性高血糖引起的代谢环境异常所致,但其发生受遗传因素的调控,被认为是人类复杂疾病的经典案例,可归因于遗传因素、环境因素及其之间的相互作用结果。遗传学对DR发生发展的研究已取得了一定成果,但具体的致病基因及其发病机制仍尚未明确。本研究针对目前已确定的潜在DR易感基因及其多态性进行综述,为进一步研究DR致病基因及其发病机制提供参考。     

血脂、血压对早期糖尿病视网膜病变进展的影响

目的探讨血脂、血压对早期糖尿病视网膜病变（DR）进展的影响。方法收集DR-0期,轻、中、重度非增生性糖尿病视网膜病变（NPDR）各20例,对照组30例,记录血脂、血压在不同分组中的测量值,分析其与早期DR发生发展的关系。结果 DR组的收缩压（SBP）、胆固醇（CHO）、甘油三酯（TG）明显高于正常对照组,而高密度脂蛋白（HDL）则低于对照组;且TG与DR的病变程度呈显著正相关。结论 CHO、TG是DR的危险因素,HDL是DR的保护因素,且TG可能与DR的发展有相关性。     

Epidemiology, risk factors and management of paediatric diabetic retinopathy

Diabetic retinopathy (DR), a common complication of both type 1 and type 2 diabetes, is rarely expressed at a level greater than background retinopathy during childhood and adolescence. Epidemiological studies in paediatric diabetic patients together with data from the Diabetes Control and Complications Trial have demonstrated the importance of glycaemic control in delaying or preventing the development of DR; thus, the incidence of DR has declined somewhat over the past two decades. Both prepubertal and postpubertal years with diabetes contribute to the overall probability of DR development. In addition to duration of disease and degree of glycaemic control, other risk factors for DR development include elevated blood pressure, lipid profiles, serum levels of advanced glycation endproducts, evidence for early stage atherosclerosis, increased calibre of retinal blood vessels and several genetic factors, such as enzymes involved in glucose and lipid metabolism. Annual screening is recommended, with mydriatic stereoscopic fundus photography being the most sensitive detection method. Both pathophysiology and treatment in paediatric populations are essentially the same as described for adult populations, with treatment usually not required until adulthood is reached.     

Nuevas pautas de tratamiento y seguimiento en pacientes con degeneración macular asociada a la edad exudativa

Intravitreal ranibizumab (Lucentis^®) injections are the treatment of choice in patients with exudative macular degeneration. In the last few years, several treatment and follow-up strategies have been evaluated with the aim of optimizing the safety and efficacy of this drug. In routine clinical practice, the Pro Re Nata (PRN) and treat-and-extend protocols or variants of the FUSION regimen have been used. PRN protocols are based on regular patient follow-up and on retreatment when there is evidence of reactivation of the lesion, basically determined by loss of visual acuity and persistent or recurrent macular fluid on optical coherence tomography. Treat-and-extend or FUSION protocols are based on early retreatment of the lesion before reactivation occurs with the aim of avoiding the irreversible visual loss that can occur in disease recurrences.There is no ideal treatment and follow-up protocol that could be used as an alternative to the monthly regimen and be applied and reproduced in all patients. Consequently, intravitreal ranibizumab therapy should be individualized in each patient.     

认识糖尿病视网膜病变临床研究热点难点，探索优化未来临床研究方向

糖尿病视网膜病变（DR）临床研究涉及的领域庞大,选题方向广泛。DR与全身疾病的关系、发生发展的影响因素以及早期筛检发现手段、减少延缓DR发生发展的措施以及改进提高治疗效果的干预手段等一些围绕改善DR治疗效果的临床研究是目前DR临床研究的热点。但由于DR发病机制复杂,影响其发生发展的因素众多,导致DR防控周期长,涉及层面复杂以及DR临床研究中不易剔除的混杂因素较多均是DR临床研究的难点。从长远角度看,延缓DR发生和进展、建立高效实用的防控体系等方面的研究是未来应着重关注的研究方向。     

Evidence-Based Treatment of Diabetic Retinopathy

ABSTRACT

Diabetic retinopathy (DR) is the most frequent microvascular complication from diabetes and requires annual screening and at least annual follow-up. A systemic approach to optimize blood glucose and blood pressure may halt progression to severe stages of DR and obviate the need for ocular treatment. Although there is evidence of benefit from fenofibrate or intravitreous antiVEGF treatment for eyes with nonproliferative DR (NPDR), these therapies are not standard care for NPDR at this time. Some patients with severe NPDR, especially those with type 2 diabetes, benefit from early panretinal photocoagulation (PRP). Once DR progresses to proliferative DR (PDR), treatment is often necessary to prevent visual loss. PRP remains mainstay treatment for PDR with high-risk characteristics. However, intravitreous antiVEGF injections appear to be a safe and effective treatment alternative for PDR through at least two years. Vitreoretinal surgery is indicated for PDR cases with non-clearing vitreous hemorrhage and/or tractional retinal detachment.     

黄斑区视网膜深层微血管变化对糖尿病性黄斑水肿的影响

近年来光学相干断层扫描血管成像 (OCTA)作为一项新型的成像技术,通过探测血管内移动的信号来使血流显影,其量化血管参数的优势使其可监测糖尿病视网膜病变(DR)发生发展过程中视网膜毛细血管的变化,从而预测DR的发生发展。许多研究表明,早期DR患者各层视网膜血管参数均发生了变化,且深层毛细血管丛的变化较浅层毛细血管丛明显,而这种变化在糖尿病性黄斑水肿（DME）中更为显著,由此推测黄斑水肿首先发生于深层毛细血管丛中。而玻璃体内注射抗血管内皮生长因子(VEGF)药物后能明显减轻黄斑水肿,提高患者视力,影响黄斑区视网膜微血管。本文通过总结应用OCTA观察DR和DME患者病程发展中以及抗 VEGF 治疗后黄斑区视网膜深层微血管的变化,从深层微血管的改变对DME发生发展及预后的影响进行综述。