【作者】 孙堂胜；

【导师】 张卯年；

【作者基本信息】 中国人民解放军军医进修学院 ， 眼科学， 2009， 博士

【摘要】 糖尿病（diabetes mullitis,DM）已经成为一个全球性的疾病,达到近2.4亿,成为全球性的重大负担。作为糖尿病的主要并发症之一-糖尿病视网膜病变（diabetic retinopathy,DR）已成为糖尿病患者致盲的首要原因。DR的病理学改变包括糖尿病微血管病变和糖尿病神经视网膜的异常。相对于国内外糖尿病视网膜微血管病变的基础和临床研究,糖尿病神经视网膜功能的评价则十分薄弱。DR的发生不仅预示着视功能损害的开始,同时提示其结构基础-视网膜的功能也将不可逆转,所以早期获得视功能相关数据非常关键。如何早期掌握视功能的变化以及这些变化与糖尿病病情关系的信息将有助于我们及时采取治疗干预措施,遏制DR的发生和发展,从而挽救和保护糖尿病患者的视功能。我们从这一思路出发,首先从视觉对比敏感度（contrastsensitivity,CS）、色觉（colour vision）、多焦视网膜电图（multi-focalelectroretinogram,mERG）等方式了解糖尿病早期患者的视功能情况,不仅阐明这些手段在评估糖尿病患者视功能变化中的重要作用,而且还可以揭示与反映糖尿病病情的指标之间的密切关系。我们将从中筛选出与视功能损害相关的指标,为临床治疗提供全面而准确的依据。目的1.研究无临床可见视网膜病变、矫正视力完全正常的糖尿病患者视觉对比敏感度的变化特征;2.分析糖尿病患者早期色觉损害的特征;3.探讨mERG在糖尿病患者早期的改变规律;4.了解糖尿病患者早期视觉对比敏感度、色觉以及mERG的异常变化与糖尿病病程、年龄及相关的生化指标的内在关系。方法1.视觉对比敏感度的测试:应用美国OPTEC 6500型对比敏感度测试仪进行糖尿病患者（72人,126眼）及对照组（45人,78眼）的无眩光条件下5个频率的远、近距离的视觉对比敏感度测试,记录统计正常组及糖尿病患者5个频率的视觉对比敏感度范围并比较两组之间的差异特点,分析糖尿病患者年龄、病程、胰岛素使用时间及部分生化指标与视觉对比敏感度异常变化的关系;2.色觉检查:采用法国Famsworth Munsell-100型色觉测试仪,分别对糖尿病组（42人,74眼）及对照组（45人,78眼）进行色觉测试,分析两组之间在总错误得分（total error score,TES）、√TES以及红、绿、蓝色觉的错误得分及其平方根之间的差别,同时了解糖尿病患者年龄、病程、胰岛素使用时间及部分生化指标与色觉异常变化的关系。3.mERG检查:采用德国Roland RETI port21型综合视觉电生理仪,分别对糖尿病组（19人,34眼）及对照组（17人,30眼）按同样步骤和参数进行检查,对其一阶响应结果进行分析,比较两组间在N₁波和P₁波振幅上的差异,并探讨糖尿病患者年龄、病程、胰岛素使用时间及部分生化指标与mERG异常变化的关系。结果1.视觉对比敏感度:（1）糖尿病组与对照组视觉对比敏感度各频率无论在远距离还是近距离均存在显著性差异（P＜0.03）,高频区更为明显;（2）在糖尿病组及对照组,视觉对比敏感度同一频率在远、近距离之间皆存在极显著的差别（P＜0.00）;（3）不同年龄组CS值的差异集中体现在高频区,而不同病程组之间的差异几乎是全频段的,胰岛素的使用时间1月内与高频区极显著相关;（4）不同生化指标与视觉对比敏感度不同频率的变化密切相关,尤其在与快速尿蛋白/肌酐比值（albumin/cretinine ratio,ACR）的关系上出现全频段的极显著性相关。2.色觉:（1）糖尿病组与对照组在红、绿、蓝色觉的错误得分及其平方根之间均存在极显著性差异（P＜0.005）,其中红色觉损害最为显著而蓝色觉最为轻微。两组在TES以及√TES方面无差异;（2）色觉损害主要与糖尿病患者年龄和病程相关;（3）总蛋白（total protein,TP）和空腹血糖（fasting bloodglucose,FBG）分别与蓝色觉和绿色觉损害具有显著相关性。3.mERG:（1）糖尿病患者各波振幅普遍降低而潜伏期延长,主要表现在P₁波振幅和N₁波潜伏期上;（2）mERG的异常变化与糖尿病患者年龄以及胰岛素使用时间相关;（3）部分生化指标如FBG、糖化血浆蛋白等几乎与各环别P₁波的潜伏期的改变相关。结论1.视觉对比敏感度在糖尿病患者早期出现全频段CS值下降,其中多数患者高频段CS值的下降明显,并与年龄及多项生化指标密切相关,是评价糖尿病患者早期视功能的敏感指标。快速ACR升高可能属于影响糖尿病患者早期视觉高频段对比敏感度水平的危险因素;2.红色、绿色及蓝色觉在糖尿病患者早期即出现损害,其中红色、绿色觉损害更为显著,表现在近半数的患者中,并与年龄、病程等密切相关,可以作为糖尿病患者早期视功能评价的敏感指标。TP和FBG的升高可能分别是糖尿病患者早期蓝色觉和绿色觉损害的危险因素;3.mERG在糖尿病患者早期出现异常改变,损害的主要特征是P₁波振幅的降低和N₁波潜伏期的延长,应为糖尿病患者早期视功能评价的敏感指标。FBG和糖化血浆蛋白的升高可能与糖尿病患者早期mERG的P₁波潜伏期的延长密切相关。更多还原

【Abstract】 Diabetes mullitis（DM）has become a global disease.Currently there are nearly 240 million diabetic patients,a main burden in the world.As one of major complications of diabetes-diabetic retinopathy（DR） has become one of the leading causes of blindness.Pathological changes of DR includes diabetic microangiopathy and diabetic retinal nerve abnormalities.Relative to basic and clinical researches on diabetic microangiopathy home and abroad,evaluation on diabetic retinal neurological function is very weak.DR indicates the occurrence of impairment of visual functions and the retinal function will be irreversible.So early representation data of the visual functions of retinal is very critical.How to master the early changes in visual functions as well as its relation to diabetes condition will help us to take timely treatment intervention to curb the occurrence and development of DR,to rescue and protect visual functions in diabetic patients.From these we choose visual contrast sensitivity（CS）,colour vision and multifocal electroretinogram（mERG） as research tools,not only to clarify their important role on assessment of visual functions,but to reveal the relationship between condition of diabetes and these indicators.We will filter out the indicators which are closely related to the impairment of visual functions to provide clinical comprehensive and accurate data.Purposes1.To study the changing characteristics and scopes of contrast sensitivity values in diabetic patients with normal visual acuity and without DR;2.To investigate the characteristics of color vision damage in the different diabetic conditions;3.To explore the change principals in mERG in early diabetic patients;4.To probe the intrinsic relations between CS,color vision,mERG changes and some biochemical indicators which closely associated with DM.Methods1.CS:CS values were measured in 72 diabetic patients（126 eyes） and 45 healthy persons（78 eyes）,non-glare of five frequencies,both in far- and near-distance,with application of OPTEC 6500 tester.Compared CS values in each frequency between these two groups and disvovered the relationship between CS values changes and age,duration time of DM,application time of insulin & some biochemical parameters;2.Color Vision:Color perception was measured in 42 diabetic patients（74 eyes） and 45 healthy persons（78 eyes） with use of Farnsworth Munsell-100 hue tester respectively and analysed difference on total error score（TES）,√TES as well as red,green,blue error scores and their square roots,the relationship were determined between color damage and age,duration time of DM,application time of insulin & some biochemical parameters;3.mERG:mERG was detected in 19 diabetic patients（34 eyes） and 17 healthy persons（30 eyes） with application of the Roland RETIport21 visual electrophysiology instruments,according to the same procedure and parameters. Selected the first-kernal-order（FOK） response results as analysis data.Analysed the difference on amplitude and latency of P₁ & N₁ wave between two groups,and their relation to age,duration time of DM,application time of insulin & some biochemical parameters.Results1.CS:（1） There were significant difference（P＜0.03） between diabetic group and control group on CS values in both far- and near-distance,espacially in high frequencies;（2） There were significant difference（P＜0.00）between far- and near-distance CS values in both diabetic group and normal controls;（3） Significant differences existed in different ages mainly in high-frequencies, different diabetes duration almost in full frequencies and application time of insulin within 1 month only in high-frequency section;（4） CS values closely related with many biochemical markers,especially with rapid ACR （albumin/cretinine ratio ）,very significant on full range of frequencies;2.Color Vision:（1） There was significant difference（P＜0.005） between two groups on red,green,blue error scores and their square roots.The red perception damage was the most significant and the blue was most minor.No difference between the TES and√TES;（2） Color damage mainly related with age and duration time;（3） TP and FBG closely related with damage of blue and green perception respectively;3.mERG:（1） The wave amplitude reduced and the latency extended in diabetic patients,mainly in P₁ amplitude and N₁ latency;（2） These changes related with age and application time of insulin;（3） Some biochemical parameters such as FBG,glycosylated plasma protein etc.mainly associated with the latency of P₁ wave in every cycle.Conclusions1.Visual contrast sensitivity function declines early in full frequencies in diabetic patients,especially in high frequencies,and relate to many biochemical parameters,can be a sensitive marker in evaluating the functions of retina.Rapid ACR elevation can be a risk factor with impact on early CS values in high-frequencies;2.Color damage happens in red,green and blue in early diabetic patients, especially in red,green perception in nearly 50%patients and relate closely to age, duration time of DM,so can be sensitive indicators in early evalution of visual functions in diabetic patients.TP and FBG can be risk factors in leading to blue and green perception early damage in diabetic patients;3.mERG changes early in diabetic patients.P₁ wave amplitude fall and N₁ wave latency extension are main features of damage in retinal functions,can be sensitive indicators in early evalution of visual functions in diabetic patients. Elavation of FBG and glycosylated plasma protein have close relation to early P₁ wave latency extension in diabetic patients.更多还原