Diabetic retinopathy and diabetic macular edema: pathophysiology,screening, and novel therapies

Diabetic retinopathy (DR) and diabetic macular edema (DME) are leading causes of blindness in the working-age population of most developed countries. The increasing number of individuals with diabetes worldwide suggests that DR and DME will continue to be major contributors to vision loss and associated functional impairment for years to come. Early detection of retinopathy in individuals with diabetes is critical in preventing visual loss, but current methods of screening fail to identify a sizable number of high-risk patients. The control of diabetes-associated metabolic abnormalities (i.e., hyperglycemia, hyperlipidemia, and hypertension) is also important in preserving visual function because these conditions have been identified as risk factors for both the development and progression of DR/DME. The currently available interventions for DR/DME, laser photocoagulation and vitrectomy, only target advanced stages of disease. Several biochemical mechanisms, including protein kinase C-beta activation, increased vascular endothelial growth factor production, oxidative stress, and accumulation of intracellular sorbitol and advanced glycosylation end products, may contribute to the vascular disruptions that characterize DR/DME. The inhibition of these pathways holds the promise of intervention for DR at earlier non-sight-threatening stages. To implement new therapies effectively, more individuals will need to be screened for DR/DME at earlier stages-a process requiring both improved technology and interdisciplinary cooperation among physicians caring for patients with diabetes.     

Current intravitreal pharmacologic therapies for diabetic macular edema

Introduction: Diabetic retinopathy is the leading cause of vision loss in working-age adults; it is a highly prevalent cause of vision loss overall and has a potent impact on the quality of life in those with diabetes mellitus and public health in general. Diabetic macular edema (DME) is the most common cause of vision loss from diabetic retinopathy. In patients with diabetes mellitus, chronic hyperglycemia leads to activation of the inflammatory cascade and retinal capillary damage that result in microaneurysm formation in the retina. In addition to the possibility of associated ischemia, microaneurysms are hyperpermeable; the resultant loss of the blood–retinal barrier leads to vision loss if consequent edema involves the center of the fovea. The standard of DME therapy for >25 years was focal laser photocoagulation applied to or near the microaneurysms. However, results from clinical trials of intravitreal vascular endothelial growth factor (VEGF) blockers and corticosteroids for the treatment of DME have led to a dramatic paradigm shift away from laser therapy to primary treatment with these pharmacologic agents. Methods: Medline literature search of approaches for treating DME. Results: Intravitreal pharmacologic treatments with anti-VEGF agents and corticosteroids have recently been shown to be superior to laser treatment of DME. Conclusion: The existence of pharmacologic treatment of DME, shown to be superior to laser monotherapy, has created a seismic change in the approach of treatment of these patients. This review provides a summary of the therapies and the rationale regarding the current pharmacologic therapy of DME.     

曲安奈德治疗糖尿病黄斑囊样水肿临床效果观察

目的 观察糖尿病黄斑囊样水肿运用曲安奈德(TA)后视力及黄斑厚度变化.方法 选择经临床及眼底荧光血管造影和视网膜光学相干断层扫描仪(OCT)确诊的黄斑囊样水肿患者22例25眼,接受玻璃体腔内注射TA 4ms/0.1 ml,在1周、1月、2月及3月时分别检查患者视力、OCT及眼压等.结果 23眼视力有明显提高,OCT检查黄斑犀度有显著降低(P<0.01),无并发症发生.结论 玻璃体腔内注射TA可显著减轻糖尿病性黄斑囊样水肿,有效改善患者的视力,并发症较少.     

激光治疗糖尿病性黄斑水肿的理论与应用

目的糖尿病性黄斑水肿(diabetic macular edema,DME)是引起糖尿病患者视力恶化的主要原因.自激光应用于眼科以来,根据资料和研究表明激光治疗黄斑水肿可以稳定和提高患者的视力.回顾DME的病因分型、激光治疗的原理及治疗方法和治疗效果,表明激光是对DME的较为理想的治疗方式.资料来源应用计算机检索Medline 1980-01/2004-01期间与激光治疗糖尿病黄斑水肿内容相关文章,检索词"diabetic macular edema,laser",并限定文章语言种类为English.同时计算机检索中国期刊全文数据库1994-01/2004-01期间与激光治疗糖尿病黄斑水肿内容相关文章,限定文章语言种类为中文,检索词"糖尿病、黄斑水肿、激光".资料选择选择关于DME及其激光治疗的文献,国外文献100篇,国内文献50篇.在文献选择中,研究原著的选择未排除其研究是否采用了随机和盲法的设计方案.资料提炼对检索到的有关DME及其激光治疗的英文文章100篇,中文文章50篇,共150篇文章中相关信息进行综合整理.资料综合分析DME的病因分型,针对激光治疗的原理、治疗的方法、治疗的效果、治疗中需注意的问题、如何进行合理的应用激光逐一阐明.结论越来越多的研究结果表明,开展光凝治疗已成为防治糖尿病视网膜病变所致失明的行之有效的方法,黄斑水肿的患者通过激光治疗使得视力得到稳定和提高.     

A reinforcement learning approach for VQA validation: An application to diabetic macular edema grading

Recent advances in machine learning models have greatly increased the performance of automated methods in medical image analysis. However, the internal functioning of such models is largely hidden, which hinders their integration in clinical practice. Explainability and trust are viewed as important aspects of modern methods, for the latter’s widespread use in clinical communities. As such, validation of machine learning models represents an important aspect and yet, most methods are only validated in a limited way. In this work, we focus on providing a richer and more appropriate validation approach for highly powerful Visual Question Answering (VQA) algorithms. To better understand the performance of these methods, which answer arbitrary questions related to images, this work focuses on an automatic visual Turing test (VTT). That is, we propose an automatic adaptive questioning method, that aims to expose the reasoning behavior of a VQA algorithm. Specifically, we introduce a reinforcement learning (RL) agent that observes the history of previously asked questions, and uses it to select the next question to pose. We demonstrate our approach in the context of evaluating algorithms that automatically answer questions related to diabetic macular edema (DME) grading. The experiments show that such an agent has similar behavior to a clinician, whereby asking questions that are relevant to key clinical concepts.     

连续玻璃体腔内注射Bevacizumab治疗糖尿病性黄斑水肿

目的观察连续玻璃体腔内注射Bevacizumab治疗糖尿病性黄斑水肿(DME)的临床疗效及安全性。方法患者46例56眼,经眼底检查、视网膜血管荧光造影(FFA)、光学相干断层扫描(OCT)确诊为糖尿病性黄斑水肿。患者年龄26～74岁,平均(56±9)岁。治疗前平均logMAR最佳矫正视力为1.012±0.42,黄斑中心凹厚度平均(576±136)μm,分别接受连续玻璃体腔内注射Bevacizumab 1.25 mg(0.05 ml)3～5次,平均(4±1)次,每次间隔1个月。治疗后随访6～12个月,平均(9±3)个月。对比治疗前后视力、眼压、黄斑中心凹厚度及FFA改变。结果 46例患者随访6～12个月,平均logMAR最佳矫正视力提高到0.65±0.44,与治疗前比较差异有统计学意义(P<0.05)。其中36眼logMAR最佳矫正视力提高2行或以上,占64.29%。OCT示:黄斑中心凹厚度降低到(275±103)μm,与治疗前比较差异有统计学意义(P<0.05)。治疗过程中未发现严重不良反应。结论连续玻璃体腔内注射Bevacizumab 1.25 mg(0.05 ml)治疗糖尿病性黄斑水肿能明显改善视功能,减轻黄斑水肿,未发现严重不良反应。     

周细胞及Apelin在糖尿病性黄斑水肿中的作用

糖尿病性黄斑水肿（DME）是导致糖尿病性视网膜病变患者视力下降的主要原因,其中多元醇途径、己糖胺通路、糖基化终末产物等机制已被熟知。最近研究表明周细胞及Apelin在糖尿病性黄斑水肿的发生发展中也起着重要作用,因此该文就周细胞及爱帕琳肽（Apelin）在糖尿病性黄斑水肿中的作用做一综述,旨在了解更多关于DME的可能机制。     

地塞米松玻璃体内植入剂对比雷珠单抗治疗糖尿病黄斑水肿的疗效及安全性的荟萃分析

目的:比较地塞米松玻璃体内植入剂(intravitreal dexamethasone implant,IDI)和雷珠单抗治疗糖尿病黄斑水肿(diabetic macular edema,DME)的疗效和安全性,为临床治疗DME用药提供依据。方法:检索PubMed、Cochrane图书馆、Embase、Web of Science、万方数据知识服务平台、中国知网、及重庆维普中文科技期刊全文数据库中这两种药物治疗DME的临床对照试验文献,对纳入文献进行风险评估,提取文献中相关指标,采用RevMan 5.3软件进行数据分析,应用随机或固定效应模型分析异质性,检测发表偏倚。结果:共纳入符合条件的文献5篇,合计593例患者。IDI组和雷珠单抗组黄斑中心凹视网膜厚度(central macular thickness,CMT)治疗后1个月加权均数差(weighted mean difference,WMD)=.107.13;95%置信区间(confidence interval,CI):.149.44~.64.81;P<0.00001;3个月WMD=.58.10;95%CI:.88.39~.27.82;P=0.0002,IDI组患者黄斑水肿(macular edema,ME)减轻程度相比雷珠单抗组更明显,差异有统计学意义。两组患者最佳矫正视力(best corrected visual acuity,BCVA)治疗后1个月[WMD=.0.08;95%CI:.0.23~0.07;P=0.28]和3个月[WMD=.0.09;95%CI:.0.09~0.01;P=0.08]比较,差异无统计学意义。IDI组有增加白内障(OR=4.23,95%CI:1.93~9.26,P=0.0003)和升高眼压(OR=8.55,95%CI:4.63~15.81,P<0.00001)的风险,但具有较少的注射次数。结论:IDI和雷珠单抗均可改善BCVA、降低CMT,二者在视力改善方面没有差异,IDI在减轻ME方面比雷珠单抗有优势,且注射次数少,但IDI增加眼压及发生白内障的风险较雷珠单抗高。     

Exudate-based diabetic macular edema detection in fundus images using publicly available datasets

Diabetic macular edema (DME) is a common vision threatening complication of diabetic retinopathy. In a large scale screening environment DME can be assessed by detecting exudates (a type of bright lesions) in fundus images. In this work, we introduce a new methodology for diagnosis of DME using a novel set of features based on colour, wavelet decomposition and automatic lesion segmentation. These features are employed to train a classifier able to automatically diagnose DME through the presence of exudation. We present a new publicly available dataset with ground-truth data containing 169 patients from various ethnic groups and levels of DME. This and other two publicly available datasets are employed to evaluate our algorithm. We are able to achieve diagnosis performance comparable to retina experts on the MESSIDOR (an independently labelled dataset with 1200 images) with cross-dataset testing (e.g., the classifier was trained on an independent dataset and tested on MESSIDOR). Our algorithm obtained an AUC between 0.88 and 0.94 depending on the dataset/features used. Additionally, it does not need ground truth at lesion level to reject false positives and is computationally efficient, as it generates a diagnosis on an average of 4.4 s (9.3 s, considering the optic nerve localisation) per image on an 2.6 GHz platform with an unoptimised Matlab implementation.     

雷珠单抗联合激光光凝对糖尿病黄斑水肿疗效的系统评价

目的系统评价雷珠单抗联合激光光凝对糖尿病黄斑水肿的疗效。方法计算机检索PubMed、EMbase、Cochrane Library、CBM、Wang Fang Data和CNKI数据库,搜索雷珠单抗联合激光光凝治疗糖尿病黄斑水肿的相关随机对照研究,检索时限均为从建库至2016年12月。由两位研究者独立筛选文献、提取资料,并评价纳入研究的偏倚风险后,采用RevMan 5.3 软件进行Meta分析。结果共纳入7个随机对照研究,包含患者518例,眼数为556眼。Meta分析结果显示：联合组在1、3、6月最佳矫正视力的测量值均高于对照组,其差异均有统计学意义[SMD=-0.37,95%CI（0.05,0.69）,P=0.02;SMD=1.17,95%CI（0.56,1.78）,P=0.0002;SMD=2.34,95%CI（0.16,4.51）,P=0.04],且随着时间的增加,联合组的视力恢复的更多,联合组在1、3、6月中央黄斑厚度的测量值较对照组明显减少,其差异均有统计学意义[SMD=-1.34,95%CI（-2.41,-0.28）,P=0.01;SMD=-1.36,95%CI（-2.37,-0.34）,P=0.009;SMD=-1.05,95% CI（-1.34,-0.76）,P<0.00001]。结论雷珠单抗联合格栅光凝治疗治疗糖尿病黄斑水肿的效果优于单用雷珠单抗或格栅光凝,不良反应少,未见严重不良反应,值得在糖尿病黄斑水肿的治疗中应用和推广。     

玻璃体腔注射雷珠单抗治疗糖尿病性黄斑水肿病人围术期的护理

[目的]探讨玻璃体腔注射雷珠单抗治疗糖尿病性黄斑水肿病人的护理要点。[方法]选取2019年1月—2019年2月在山西省眼科医院玻璃体视网膜科收治的糖尿病性黄斑水肿病人102例(102眼),所有病人行玻璃体腔注射雷珠单抗治疗,其中2019年1月51例为对照组,2019年2月51例为研究组,对照组常规护理,术后第1天发放自制的调查表,分析影响病人心情不佳的因素,研究组在常规护理的基础上给予改进的护理干预措施,比较两组病人术后出现心情不佳的情况。[结果]研究组病人术后出现心情不佳比率明显低于对照组(P<0.001),研究组病人对预后担忧、球结膜下出血发生率低于对照组(P<0.001)。[结论]在玻璃体腔注射雷珠单抗治疗糖尿病性黄斑水肿围术期,加强病人健康教育、心理护理及并发症的护理,可降低病人术后不适率。     

羟苯磺酸钙联合康柏西普治疗糖尿病性黄斑水肿的临床效果

目的探讨羟苯磺酸钙联合康柏西普治疗糖尿病性黄斑水肿(DME)的临床效果。方法选取我院2017年5月至2019年12月收治的100例(100眼)DME患者作为研究对象,根据随机表和编盲方法将其分为对照组和观察组,每组50例(50眼)。对照组行玻璃体腔内注射康柏西普联合安慰剂治疗,观察组行玻璃体腔内注射康柏西普联合羟苯磺酸钙胶囊治疗。比较两组患者不同时间点的BCVA、CMT,记录并发症发生情况。结果治疗2、3个月后,两组的BCVA较治疗前均提高,且观察组高于对照组(P<0.05);治疗2、3个月后,两组的CMT较治疗前减小,且观察组小于对照组(P<0.05)。两组患者均未出现严重并发症。结论羟苯磺酸钙联合康柏西普治疗DME较康柏西普单一治疗效果更好,能够降低CMT及改善患者的视力水平。     

Kernel regression based segmentation of optical coherence tomography images with diabetic macular edema

We present a fully automatic algorithm to identify fluid-filled regions and seven retinal layers on spectral domain optical coherence tomography images of eyes with diabetic macular edema (DME). To achieve this, we developed a kernel regression (KR)-based classification method to estimate fluid and retinal layer positions. We then used these classification estimates as a guide to more accurately segment the retinal layer boundaries using our previously described graph theory and dynamic programming (GTDP) framework. We validated our algorithm on 110 B-scans from ten patients with severe DME pathology, showing an overall mean Dice coefficient of 0.78 when comparing our KR + GTDP algorithm to an expert grader. This is comparable to the inter-observer Dice coefficient of 0.79. The entire data set is available online, including our automatic and manual segmentation results. To the best of our knowledge, this is the first validated, fully-automated, seven-layer and fluid segmentation method which has been applied to real-world images containing severe DME.OCIS codes: (100.0100) Image processing, (170.4500) Optical coherence tomography, (170.4470) Ophthalmology