Diabetische Retinopathie

Insight into the natural course and the clinical features of diabetic retinopathy as well as advances in understanding the pathogenesis and new developments for beneficial treatments of diabetic retinopathy have broadly enlarged during recent years. It is now well accepted that chronic hyperglycemia and arterial hypertension are the most important factors for microvascular damage in diabetes. Although established treatment modalities have not yet yielded prevention of blindness due to diabetes, there is a trend toward a broader therapeutic concept for patients with diabetes including general vasoprotection. In this context, the retina plays a major role as early retinopathy earmarks the vascular high-risk patient with diabetes. Accordingly, every proven measure should be taken to avoid what still happens in evidence-based medicine: "lost in translation."     

糖尿病性角膜病变的研究进展

晚期糖尿病(diabetes mellitus,DM)患者常出现的糖尿病性视网膜病变能够被发现,而糖尿病性角膜病变(diabetic keratopathy,DK)却时常被人们忽略.近年来的许多研究表明,DK对角膜的结构、代谢、生理功能等多个方面均有重要影响.目前临床上尚无根治DK的有效疗法,现主流疗法多集中于对症治疗...     

Angiomorphology of the ciliary body in diabetic disease

The authors describe the pathological changes in the vascular structures of the ciliary body occuring in diabetes mellitus. The lesions consist of a quantitative reduction in the number of vessels and in modifications of diameter and arborisation. Changes include sectoral thinning, isolated and grouped aneuryms and marked tortuosity. These findings are thought to be constant in the diabetic patient and are probably involved in the various aspects of diabetic eye disease affecting other structures besides the ciliary body. The group of vascular changes in the ciliary body in diabetes may aptly be termed "diabetic ciliopathy".     

On the pathogenesis of diabetic retinopathy

Recent investigations of retinal vascular cells in tissue culture, animal models, and diabetic human subjects suggest several potential pathogenetic mechanisms for diabetic retinopathy. These include the enzyme aldose reductase, which appears to be responsible for basement membrane thickening in galactosemic rats (since the lesion is prevented by an aldose reductase inhibitor), and a picture, in galactosemic dogs, that closely resembles early, background diabetic retinopathy; insulin, which stimulates, and elevated glucose levels, which inhibit in vitro proliferation of retinal pericytes. Various hormones, including the sex hormone, the insulin-like growth factors and, perhaps independently, growth hormones, may influence the later stages of diabetic retinopathy. Chronic hyperglycemia appears to be the primary pathogenetic agent in diabetic retinopathy as well as in other complications of diabetes, but the different rates of onset and progression of these complications suggest that glucose acts through different biochemical pathways that are probably under different genetic control. Finally, the locus of the primary biochemical lesion in diabetic retinopathy may reside in the neuronal or glial cells of the retina, with the retinal blood vessels only secondarily involved.     

Pathophysiology of diabetic retinopathy.

After a brief analysis of the pathological picture of diabetic retinopathy, of which only the topographical distribution of the vascular lesions appears to be specific, the results obtained with 2 new methods of study of the retinal circulation, are presented. These methods are vitreous fluorophotometry and fluorometric determination of segmental retinal blood flow. Vitreous fluorophotometry has shown that a disturbance of the blood-retinal barrier, possibly functional, appears in diabetic eyes before any lesion is clinically visible in the fundus, and that there is a close correlation between the severity of the vascular lesions and higher vitreous fluorophotometry readings. Blood flow studies have shown that in diabetes the retinal blood flow increases markedly with progress of background retinopathy, decreasing finally where proliferative retinopathy, with marked arteriolar narrowing, is present. On the basis of these findings a working hypothesis for the pathogenesis of diabetic retinopathy is presented.     

On the pathogenesis of diabetic retinopathy. A 1990 update

Although most investigators now agree that chronic hyperglycemia is the basis for diabetic retinopathy, this has not been proven definitively. Even if chronic hyperglycemia is the initial common pathway leading to retinopathy and other complications of diabetes, it appears to act by different mechanisms in different tissues. The enzyme, aldose reductase, may play a major role in the development of diabetic retinopathy, but contradictory evidence exists. At the present time, results of the only study of aldose reductase inhibition and diabetic retinopathy reported in humans were negative. Another mechanism worthy of consideration is nonenzymatic glycation (glycosylation) of proteins, but there is no direct evidence of a causal role in diabetic retinopathy. Several growth factors have been identified in the retina that may promote neovascularization, and at least two inhibitors may prevent the process. There is evidence to support a role for basic and, perhaps, acidic fibroblast growth factors in retinal vasoproliferation. Transforming growth-factor beta, a peptide produced by capillary pericytes and smooth muscle cells and activated by the interaction of these cells with vascular endothelial cells, appears to be an important inhibitor of neovascularization, as is the vascular basement membrane.     

Risk factors for diabetic retinopathy in the Cree of James Bay

background The purpose of this project was to evaluate risk factors for diabetic retinopathy in the Cree population of James Bay, Ontario. methods A retrospective cohort design was employed. The cohort was made up of all known individuals who had previously been diagnosed with diabetes in the communities of Moose Factory and Moosonee, Ontario. Hypertension, body-mass index, serum lipid levels, renal function status, and hemoglobin A1C were the main exposures of interest. Values for these variables were determined from a retrospective chart review and were sought for each individual for a five-year interval beginning one year following the diagnosis of diabetes. Relative risks for the association of these variables with diabetic retinopathy were determined through both univariate and multivariate Poisson regression. The main outcome of interest in this study was the presence or absence of any diabetic retinopathy in either eye, as determined by a retinal specialist. results Significant univariate risks for the development of retinopathy included duration of diabetes, body-mass index, hemoglobin A1C, fasting blood glucose, insulin treatment, and serum cholesterol levels. In multivariate analyses, predictors of diabetic retinopathy included body-mass index, insulin treatment, and serum cholesterol levels. An increase in body-mass index reduced the risk of diabetic retinopathy (Relative Risk [RR] 0.64 per five kg/m 2 , 95% Confidence Interval [CI] 0.04 to 1.00). Insulin therapy was associated with an increased risk of retinopathy when compared to individuals on dietary therapy alone (Relative Risk [RR] 4.71, 95% Confidence Interval [CI] 1.16 to 19.16). For individuals with serum cholesterol levels above the average for the cohort, 5.2 mmol/L, the risk of retinopathy was increased (Relative Risk [RR] 2.38, 95% Confidence Interval [CI] 0.98 to 5.79). interpretation Elevated serum cholesterol, lower body-mass index and insulin treatment were all associated with an increased risk of diabetic retinopathy in the Cree of James Bay, Ontario.     

Evaluating retinal circulation using video fluorescein angiography in control and diabetic rats.

Video fluorescein angiography has been used to evaluate retinal circulatory parameters in diabetic and non-diabetic Sprague-Dawley rats. Video fluorescein angiograms were recorded from the retina using a modified retinal fundus camera following a 5 ul bolus injection of sodium fluorescein dye into the jugular vein. Retinal circulatory parameters were measured using computer assisted image analysis. These analyses were performed on 25 diabetic rats with 1 week duration of diabetes and 26 matched, non-diabetic, rats. There was a significant (p = .0001) increase in retinal Mean Circulation Time (MCT) in the diabetic group (1.83 +/- 0.40 s) compared to the control group (1.09 +/- 0.27 s). There were no significant differences in arterial or venous diameters comparing diabetic and control groups. In a separate paired experiment, measurements were made from the same animals both before and after one week duration of diabetes. A paired t-test analysis demonstrated significantly increased MCT times in the 6 diabetic animals (p = .001) while there was no significant differences detected in the 4 corresponding control animals. These results indicate that significant increases in retinal circulation times can be measured as early as 1 week after streptozotocin induced diabetes in this animal model.     

Overview of epidemiologic studies of diabetic retinopathy

Diabetic retinopathy has been an important cause of blindness in young and middle age adults in the United States. Epidemiologic studies have quantitated the risk and have described potentially causal factors associated with many ocular complications of diabetes and other facets of this disease. A review of recent advances in diagnosis, treatment, temporal trends, and health care for diabetic retinopathy was conducted. Since the early 1980's, there have been studies of the variability of diabetic retinopathy in populations around the world and subpopulations in the United States which have demonstrated the high prevalences and incidences of this condition. Observational studies and clinical trials have documented the importance of glycemic and blood pressure control in the development and progression of this disease. There are some differences in the importance of confounders in different populations. Epidemiologic data have helped understand the importance of health care and health education in prevention and treatment of this condition. Observational studies have documented the importance of this disease on quality of life. Although there have been advances in understanding the distribution, causes, and severity of diabetic retinopathy, this is ever changing and requires continued monitoring. This is important because the increasing burden of diabetes will place a greater burden on the population and the medical care systems that will be caring for them.     

Diabetes mellitus: pathophysiology and current trends in management

Diabetes mellitus is a group of disorders that have in common abnormal insulin function resulting in disordered carbohydrate, protein and fat metabolism, the cardinal feature being elevated blood glucose levels. Acute complications include diabetic ketoacidosis, hyperosmolar non-ketotic "coma" and hypoglycemia. Long-term complications develop over several years and cause more morbidity and mortality than the acute complications. Although the pathogenesis of long-term complications is still unknown, it is likely that it relates to the abnormal metabolic state that occurs in diabetes. Current techniques of monitoring diabetes include blood glucose self-monitoring and the measurement of glycosylated hemoglobin. Management focuses on dietary adjustments (caloric amount, timing and composition), exercise and medications. Patients are encouraged to participate in comprehensive diabetes education programs to learn about new aspects of treatment and prevention of complications.     

Incipient diabetic retinopathy--insights from an experimental model

Vascular complications of chronic hyperglycemia including diabetic retinopathy are an increasing therapeutic and socioeconomic challenge. The epidemiology of diabetic eye disease has been well described, and there is as yet no clear indication for a reduction of incidence of blindness. Due to the complex multifactorial nature of the damage to diabetic vessels, it had been difficult to identify key targets for treatment and prevention. Novel techniques to study molecules and mechanisms involved in retinal vessel development and vascular cell interactions improved the understanding of retinal cell biology and pathobiology. A unifying concept has been proposed which links hyperglycemia-induced mitochondrial overproduction of reactive oxygen species with long-known biochemical alterations such as the formation of advanced glycation end products or the activation of the protein kinase C pathway. Specific inhibitors were identified that inhibited multiple biochemical abnormalities downstream of oxidative stress induced by high glucose.     

糖尿病视网膜病变相关基因多态性研究进展

糖尿病视网膜病变是糖尿病的并发症之一,严重影响人类健康和生活质量.探索并积极寻找预防和治疗的方法,是目前面临的主要问题.通过大量的流行病学调查后,发现糖尿病视网膜病变的发生和发展除了与疾病的病程、血糖控制的情况有关外,人群中个体差异的因素也十分重要.有的患者糖尿病的病程很长且血糖控制不良,但随访过程中并未发生糖尿病视网膜病变或其病变程度很轻;而有些患者虽然病程较短且血糖控制良好,但仍然发生了严重的增生性糖尿病视网膜病变,且病变呈明显的家族聚集性趋势.在排除了外界因素的干扰后,考虑发生这一现象的主要原因是由于遗传基因易感性不同所致.     

Disc swelling in an adult diabetic patient

A patient with insulin dependent adult onset diabetes presented with bilateral disc edema and minimal visual dysfunction. Initial work-up excluded an intracranial lesion, and a lumbar puncture revealed a normal opening pressure. The patient developed proliferative retinopathy, for which she received photocoagulation therapy. She subsequently developed an exacerbation and change of her disc swelling, associated with raised intracranial pressure. The differential diagnosis of diabetic papillopathy and papilledema is discussed.     

糖尿病患者眼部并发症相关知识-态度-行为分析

目的　了解２型糖尿病患者眼部并发症相关知识、态度、行为（ＫＡＰ）情况及影响因素,为相关干预提供依据。方法　问卷调查太原市社区卫生服务中心的２９６例２型糖尿病患者,内容包括一般项目和糖尿病患者眼部并发症相关知识、防治态度及行为水平,统计患者糖尿病眼病相关知识、态度及行为得分情况,运用Ｓｐｅａｒｍａｎ秩相关分析相关性,并使用多元线性回归法筛选其影响因素。结果　被调查的２型糖尿病患者眼部并发症知识得分为（６．９３±２．３２）分,多元线性回归分析显示月收入、年龄、糖尿病病程及血糖控制水平对糖尿病眼病相关知识得分有影响,差异均有统计学意义（ｔ＝４．５６４、－３．６９０、３．８０４、２．１３１,均为Ｐ＜０．０５）。被调查患者糖尿眼病防治态度得分为（２３．６４±７．７４）分,大多数被调查的糖尿病患者对于社区开展糖尿病眼部并发症防治工作态度积极,多元线性回归分析显示,文化程度对得分有影响,差异有统计学意义（ｔ＝４．９４４,Ｐ＜０．０５）。被调查的糖尿病患者眼部并发症的防治行为得分为（１．８０±０．６２）分,多元线性回归分析显示,月收入、年龄和病程对防治行为得分有影响,且差异有统计学意义（ｔ＝４．０９８、－２．５５２、３．２９９,均为Ｐ＜０．０５）。对ＫＡＰ得分行Ｓｐｅａｒｍａｎ秩相关性分析显示,知识和态度的相关系数为０．３００,态度和行为的相关系数为０．２１９,知识和行为的相关系数为０．４６６,三者均具有统计学意义（均为Ｐ＜０００１）,存在正相关。结论　月收入低、文化程度低、年龄偏大、糖尿病病程长、血糖控制不良的糖尿病患者是今后社区宣传糖尿病眼病知识并进行行为干预的重点对象。加强科室间合作、促进糖尿病患者定期眼部检查是今后社区开展的一项切实有益的工作。     

糖尿病视网膜病变危险因素与预防研究进展

糖尿病视网膜病变（diabetic retinopathy,DR）是糖尿病（diabetes mellitus,DM）的常见慢性并发症之一,属于微血管病变,是工作人群及中老年人视力减退甚至导致失明的主要原因。1/3~1/2的糖尿病患者同时伴有视网膜病变,DR与糖尿病病程、高血糖、高血压及高血脂等危险因素均密切相关。个体血糖和血压的最优控制仍然是预防DR发生和阻止病变进展的基石,抗血管内皮因子治疗被认为是目前最有效的糖尿病性黄斑水肿的治疗方案。这些有效的防治手段,患者及医生意识的提高,定期筛查DR,将有效改善DR患者的预后,减少因DR导致失明患者的人数,进一步提高患者的生存质量。     

Perspectives on diabetic retinopathy

PURPOSE: To review the evolution of the understanding of diabetic retinopathy (DR) and methods of treating DR, the present clinically relevant practice for eye disease in patients with diabetes mellitus, and trends in clinical patient care over the next 3 to 5 years. DESIGN: Tabular review and presentation of clinical trials contributing to the understanding and treatment of DR and the author's philosophy of care for the patient with diabetes. RESULTS: Diabetic retinopathy is a microvascular complication of diabetes mellitus that is a significant cause of new-onset blindness. The Diabetic Retinopathy Study was the first multicentered, randomized, clinical trial in ophthalmology. This study provided the scientific evidence for treatment of DR with scatter (panretinal) photocoagulation, and led to the funding of other multicentered clinical trials, including the Early Treatment Diabetic Retinopathy Study, which greatly elucidated the natural history of DR and firmly established laser photocoagulation as treatment for proliferative diabetic retinopathy (PDR) and diabetic macular edema. The Diabetes Control and Complications Trial and United Kingdom Prospective Diabetes Study established the value of intensive glycemic control in reducing the risk of onset and progression of DR and other microvascular complications of diabetes. CONCLUSIONS: Severe vision loss and moderate vision loss from diabetes are essentially preventable with timely detection and treatments, careful long-term follow-up and comprehensive diabetes mellitus care firmly based on clinical evidence. Future treatments, as outgrowths of further understanding of the biochemical basis of the disease, will aim at curing or preventing retinal complications from diabetes.     

Aldose reductase,ocular diabetic complications and the development of topical Kinostat®

Diabetes mellitus (DM) is a major health problem with devastating effects on ocular health in both industrialized and developing countries. The control of hyperglycemia is critical to minimizing the impact of DM on ocular tissues because inadequate glycemic control leads to ocular tissue changes that range from a temporary blurring of vision to permanent vision loss. The biochemical mechanisms that promote the development of diabetic complications have been extensively studied. As a result, a number of prominent biochemical pathways have been identified. Among these, the two-step sorbitol pathway has been the most extensively investigated; nevertheless, it remains controversial. To date, long-term pharmacological studies in animal models of diabetes have demonstrated that the onset and development of ocular complications that include keratopathy, retinopathy and cataract can be ameliorated by the control of excess metabolic flux through aldose reductase (AR). Clinically the alleles of AR have been linked to the rapidity of onset and severity of diabetic ocular complications in diabetic patient populations around the globe. In spite of these promising preclinical and human genetic rationales, several clinical trials of varying durations with structurally diverse aldose reductase inhibitors (ARIs) have shown limited success or failure in preventing or arresting diabetic retinopathy. Despite these clinical setbacks, topical ARI Kinostat^® promises to find a home in clinical veterinary ophthalmology where its anticipated approval by the FDA will present an alternative treatment paradigm to cataract surgery in diabetic dogs. Here, we critically review the role of AR in diabetes mellitus-linked ocular disease and highlight the development of Kinostat^® for cataract prevention in diabetic dogs. In addition to the veterinary market, we speculate that with further safety and efficacy studies in humans, Kinostat^® or a closely related product could have a future role in treating diabetic keratopathy.     

光学相干断层扫描血管成像在糖尿病微血管病变中的应用

糖尿病视网膜病变(DR)和糖尿病肾病(DN)是糖尿病患者最常见、最严重的两大微血管并发症，是引起致盲和终末期肾病的主要原因。视网膜血管是糖尿病早期常见的损害靶点，也是人体血管系统中唯一可直视的活体血管，其形态结构或功能的变化可直接或间接反映糖尿病引起的微血管病变。特别是近年来光学相干断层扫描血管成像(OCTA)这一新型、无创技术的发展，在血管成像分辨率、血管深度以及血管形态方面都有新的突破，并能提供客观的定量数据，在糖尿病微血管病变中具有一定应用价值。因此，本文旨在对OCTA及其在糖尿病微血管病变中的应用作一综述。     

Lutein prevents cataract development and progression in diabetic rats

Background  Diabetes mellitus is a heterogeneous metabolic disorder characterized by hyperglycemia. It is often associated with complications, such as cataracts. Cataract, characterized by cloudiness or opacity of the eye lens, is the leading cause of blindness worldwide. Methods  The present study investigated the effect of lutein, alone or combined with insulin on the progression of eye lens opacities in streptozotocin-diabetic rats for a period of 12 weeks. Tissue markers of oxidative stress were also determined at the end of the experiment. Results  Herein we demonstrate that lutein treatment prevents the development and progression of cataracts (0 eyes with mature cataract, and ten out of 16 eyes with clear lenses in the lutein-treated diabetic animals group, vs. seven and three eyes in the non-treated diabetic group, respectively). Lipid peroxidation is significantly increased in diabetic lens (up to three-fold); lutein and insulin, alone or in combination, are able to prevent this alteration. Only insulin and lutein together could prevent the diabetes-induced decrease of glutathione content. Conclusions  The combined treatment with lutein and insulin is useful in preventing the development of cataracts in streptozotocin-induced diabetic rats, supporting its utility in diabetes management, especially when a tight metabolic control is difficult to achieve.