Corneal markers of diabetic neuropathy

Diabetic neuropathy is a significant clinical problem that currently has no effective therapy, and in advanced cases, leads to foot ulceration and lower limb amputation. The accurate detection, characterization and quantification of this condition are important in order to define at-risk patients, anticipate deterioration, monitor progression, and assess new therapies. This review evaluates novel corneal methods of assessing diabetic neuropathy. Two new noninvasive corneal markers have emerged, and in cross-sectional studies have demonstrated their ability to stratify the severity of this disease. Corneal confocal microscopy allows quantification of corneal nerve parameters and noncontact corneal esthesiometry, the functional correlate of corneal structure, assesses the sensitivity of the cornea. Both these techniques are quick to perform, produce little or no discomfort for the patient, and are suitable for clinical settings. Each has advantages and disadvantages over traditional techniques for assessing diabetic neuropathy. Application of these new corneal markers for longitudinal evaluation of diabetic neuropathy has the potential to reduce dependence on more invasive, costly, and time-consuming assessments, such as skin biopsy.     

Corneal epithelium in diabetic patients

The corneal epithelia of phakic control (n = 13), aphakic control (n = 10), diabetic phakic (n = 10), and diabetic aphakic patients (n = 13) were surveyed under a wide-field specular microscope with a special contact lens. In control patients, the corneal epithelium showed relatively hexagonal cells, which we divided into three groups: bright cells, medium-bright cells, and dark cells. These epithelial cells displayed a smooth-surface configuration. In diabetic phakic patients, the epithelium seemed almost normal, with slightly more irregularity. In diabetic aphakic patients, the epithelium appeared larger. The cells were irregular and easy to distinguish from normal cells. Morphometric analysis showed that the mean cell areas of phakic control, aphakic control, diabetic phakic, and diabetic aphakic patients were 648 +/- 152, 643 +/- 125, 658 +/- 146, and 821 +/- 203 microns 2, respectively. The increase in the average cell area in diabetic aphakic patients was statistically significant. Although no apparent changes of the epithelium could be detected in the diabetic corneal epithelium under biomicroscopy, abnormalities that could be evaluated by specular microscopic images and morphometric analysis were observed.     

Corneal endothelium after photocoagulation in diabetic patients

The corneal endothelium was photographed through a wide-field specular microscope in 38 eyes, in 20 successive diabetic outpatients receiving laser therapy because of underlying proliferative or background retinopathy. Areas of 100 individual endothelial cells from each central cornea were analysed using a digitizer. No statistically significant correlations were observed between mean cell areas or standard deviations of mean and total amount of previous laser energy received. Laser therapy or the type of diabetes did not seem to cause statistically significant changes in the endothelial cell areas examined.     

Corneal epithelial barrier function in diabetic patients

PURPOSE: To evaluate the corneal epithelial barrier function in diabetic patients. METHODS: In 29 eyes of 29 diabetic patients and 55 eyes of 55 nondiabetic controls, corneal epithelial permeability to fluorescein was measured using an anterior fluorophotometer. The average fluorescein concentration in the central cornea was compared between diabetic patients and controls. Multiple regression analysis was used to assess the factors that affect corneal epithelial barrier function in diabetic patients. RESULTS: The average fluorescein concentrations in diabetic patients and nondiabetic controls were 44.1 +/- 25.3 ng/mL and 29.9 +/- 19.8 ng/mL (mean +/- SD), respectively (P = 0.0057, unpaired t test). An explanatory variable relevant to the impaired corneal epithelial barrier function was the serum hemoglobin A1c (HbA1c) concentration (standardized partial regression coefficient = 0.466, P = 0.0163). CONCLUSIONS: The corneal epithelial barrier function is impaired in diabetic patients. Diabetic patients with higher serum HbA1c levels are more predisposed to impaired barrier function in the corneal epithelium.     

Assessing corneal nerve structure and function in diabetic neuropathy

The accurate detection and quantification of human diabetic peripheral neuropathy are important to define at-risk patients, anticipate deterioration and assess new therapies. Two emerging ophthalmic techniques, namely, corneal confocal microscopy and corneal aesthesiometry, demonstrate the ability to diagnose, quantify severity and assess therapeutic benefit in diabetic peripheral neuropathy. Corneal confocal microscopy allows quantification of corneal nerve morphology and non-contact corneal aesthesiometry assesses corneal sensitivity. The present review provides a detailed critique of the rationale, practical application in terms of the instruments used to capture images and the basis on which images are interpreted and analysed. We also critically evaluate how these two new non-invasive ophthalmic tests can be deployed to diagnose diabetic and other peripheral neuropathies.     

糖尿病视网膜病变光凝术后角膜知觉的改变

目的 探讨糖尿病视网膜病变患者在全视网膜光凝术后的角膜知觉改变及影响因素。方法 32例(32只眼)糖尿病视网膜病变患者应用倍频ND：YAG激光行全视网膜光凝,光凝斑大小：200～300／μm,光凝时间：0．2～0．4秒,光凝斑强度以达到中等强为标准。采用Cochet--Bonnnnet角膜知觉测量仪测量光凝前及光凝后1、2、3、4、5、6周及2个月的角膜知觉。结果 糖尿病视网膜病变患者术前的角膜知觉为2．27cm,术后1、2、3、4、5、6周及2个月的角膜知觉分别为1．42cm、1．60cm、1．58cm、1．92cm、1．71cm、2．19cm和2．23cm。与术前相比,术后1～5周的角膜知觉减退值与术前的角膜知觉的相关系数为0．82。结论 糖尿病视网膜病变行全视网膜光凝后的角膜知觉有明显减退,在光凝后6周恢复至术前水平,角膜知觉的减退值与光凝的范围及术前的角膜知觉有关。     

非增生型糖尿病视网膜病变合并糖尿病视神经病变的临床分类及表现

目的 观察非增生期糖尿病视网膜病变(NPDR)合并糖尿病视神经病变(DON)的临床分类及表现.方法 经荧光素眼底血管造影(FFA)检查确诊为NPDR的224例患者440只眼纳入研究.采用光相干断层扫描(OCT)检查观察视盘形态,测量视盘周围视网膜神经纤维层(RNFL)厚度.同时检测糖化血红蛋白(HbA1C)、血脂水平等全身相关指标.根据检查结果将合并DON的患者作为DON组,其余未合并DON的患者作为对照组.DON组患者进一步分为糖尿病视盘病变(DP)、缺血性视神经病变(AION)及视神经萎缩等3个亚组.观察DP、AION、视神经萎缩的发病率.分析各组间平均RNFL厚度及全身相关指标的差异.结果 224例440只眼中,合并DON者14例19只眼,占患眼的4.3％;未合并DON者210例421只眼,占患眼的95.7％.DON组14例19只眼中,DP 2例2只眼,占患眼的10.5％ AION 8例12只眼,占患眼的63.2％;视神经萎缩4例5只眼,占患眼的26.3％.DP组患眼均无明显视网膜病变.AION在无明显视网膜病变、轻度、中度、重度NPDR期的发病率比较,差异无统计学意义(x2=0.019,P＞0.05).与对照组比较,AION组视盘垂直径、水平径及视盘杯盘比(C/D)比值均较小,差异均有统计学意义(t=-2.425,-3.432,-3.871; P＜0.05);糖尿病病程明显延长,差异也有统计学意义(t=2.320;P＜0.05).结论 NPDR可发生DP、AION、视神经萎缩3种病变.AION患者视盘垂直径、水平径及视盘C/D比值均较小,糖尿病病程明显延长.     

鼠神经生长因子对糖尿病性视神经病变的疗效分析

目的：探讨鼠神经生长因子(mouse nerve growth factor,M-NGF)治疗糖尿病性视神经病变(DON)的疗效及安全性。

方法：糖尿病性视神经病变患者67例115眼,根据是否需要激光视网膜光凝治疗分为两组,每组随机分为常规治疗组和M-NGF治疗组,均给予常规治疗,M-NGF治疗组加用M-NGF,疗程3wk。治疗后随访2mo,比较各组患者治疗后视力、视野恢复情况,并观察M-NGF治疗的安全性。

结果：在不需要激光视网膜光凝组,常规治疗和M-NGF治疗的总有效率分别为71.4%和94.7%,后者总有效率高于前者(P<0.05); 在需要激光视网膜光凝组,常规治疗和M-NGF治疗的总有效率分别为73.0%和93.3%,后者总有效率高于前者(P<0.05); 在激光组和非激光组,治疗效果无明显统计学差异(P>0.05)。除个别患者注射部位出现局部疼痛、红肿硬结外,未见其它不良反应。

结论：M-NGF治疗DON安全、有效,值得临床推广应用。     

糖尿病周围神经病变患者干眼的临床特征分析

目的:探讨糖尿病周围神经病变(DPN)患者泪膜功能的改变及干眼症状特征。方法:病例对照研究。选取存在泪膜异常的2型糖尿病(T2DM)患者59例59眼,以是否存在DPN分为T2DM组31例31眼和DPN组28例28眼,另选择符合泪膜异常标准且无糖尿病的患者33例33眼作为无T2DM组。对三组患者进行眼表疾病指数(OSDI)量表评分、泪膜破裂时间(BUT)、角结膜荧光素钠染色(FL)评分、泪液分泌试验(SchirmerⅠ)、红外线睑板腺照相。结果:各组间BUT结果有差异(F=9.43,P<0.01),无T2DM组、T2DM组和DPN组两两比较均有差异(P<0.05);各组间SchirmerⅠ及FL阳性率比较无差异(P>0.05);各组间睑板腺缺失评分有差异(χ2=8.433,P<0.05),T2DM组与无T2DM组比较无差异(P>0.05),DPN组与无T2DM组、T2DM组比较均有差异(P<0.05);各组间OSDI量表评分比较有差异(P<0.05),两两比较,T2DM组与无T2DM组比较无差异(P>0.05),DPN组与无T2DM组、T2DM组比较均有差异(P<0.05)。结论:合并DPN的T2DM患者较不伴发DPN的T2DM患者及无T2DM患者BUT更短、睑板腺缺失更重,但干眼症状更不明显,应密切关注和随访DPN患者的眼表异常。     

Corneal transplantation in a patient with congenital sensory neuropathy.

We describe penetrating keratoplasty for corneal scarring in a patient with congenital sensory neuropathy and repeated self-mutilation. This patient underwent a successful penetrating keratoplasty but suffered a series of postoperative complications necessitating three repeat grafts. Some of these complications were attributable to decreased corneal sensation while others were caused by self-mutilation. Since his last penetrating keratoplasty 4 years ago, this patient has had functional visual acuity.     

Corneal nerve access in monkeys

Summary Electron microscopical examination of corneal nerves in rhesus and cynomolgous monkeys revealed that limbal, subepithelial nerves gained direct access to the corneal epithelium. Epithelial axons occurred singly and infrequently and they were confined to the basal layer of cells.All nerves of the stroma terminated within the layer and rami perforans were not found. The apparent barrier to nerve passage presented by Bowman's layer in monkeys was discussed in relation to primates in general.The isolation of stromal and epithelial nerve fibres confirms that terminals occur in both layers and their respective potential for excitation was briefly discussed.This paper was presented in part at the Sixth Annual Meeting of the European Club for Ophthalmic Fine Structure in Paris, France, on March 31 and April 1, 1978     

糖尿病患者白内障术后角膜形态变化

目的探讨白内障超声乳化术对糖尿病患者角膜内皮细胞的影响及角膜厚度的变化。方法选取白内障超声乳化手术的患者107例（134只眼）分为3组：1单纯老年性白内障患者62例（65只眼）为对照组;2糖尿病患者21例（31只眼）;3合并高血压的糖尿病患者24例（38只眼）。应用角膜内皮显微镜观察手术前及术后2天、1周、1个月的中央角膜内皮密度（CCD）、变异系数（CV）、六角形细胞百分比（6A%）及中央角膜厚度（CCT）的变化。结果术前2个糖尿病组与对照组比较：CCD、CV、6A%差异无显著性（P〉0.05）,CCT差异有显著性（P〈0.05）;术后2 d、1周、1个月CCD、6A%3组均较术前下降,CV增加,差异均有显著性（均为P〈0.05）;CCT在术后2 d、1周较术前增厚,合并高血压的糖尿病组较糖尿病组进一步增厚（均为P〈0.05）;术后各时间段2个糖尿病组CCD与相应对照组无明显统计学差异（P〉0.05）,CV、CCT均高于相应对照组,6A%下降,差异均有显著性（均为P〈0.05）。结论超声乳化手术对角膜内皮及角膜厚度有影响,糖尿病患者内皮损害加重,合并高血压的糖尿病患者手术后角膜厚度增加更明显。     

2型糖尿病合并周围神经病变患者的干眼临床特征

目的:探讨2型糖尿病合并周围神经病变(DPN)患者的干眼临床特征。方法:前瞻性队列研究。收集2021-07/2022-03上海中医药大学附属曙光医院内分泌科2型糖尿病患者192例,均选右眼为观察眼,其中确诊为DPN患者122例,糖尿病无周围神经病变(NDPN)患者70例。比较两组患者眼表疾病指数量表(OSDI)评分、泪河高度、泪河宽度、角膜上皮厚度、角膜内皮细胞密度、泪液分泌试验(SⅠt)、角膜敏感度、睑板腺功能状态评分、泪膜破裂试验(BUT)、角膜荧光素钠染色评分及多伦多临床评分系统(TCSS)评分,分析2型糖尿病患者OSDI评分与TCSS评分的相关性。结果:DPN组患者干眼患病率(55眼,45.1%)显著高于NDPN组(20眼,28.6%)(χ²=5.094,P=0.024),BUT和角膜敏感度评分低于NDPN组(P<0.001),角膜染色评分和睑板腺功能评分高于NDPN组(P<0.001)。所有受试者OSDI评分与TCSS评分呈负相关(r_s=-0.233,P=0.002),同时DPN组受试者的OSDI评分与TCSS评分呈负相...     

Corneal thickness as a risk factor for visual field loss in patients with preperimetric glaucomatous optic neuropathy

PURPOSE: To determine whether central corneal thickness (CCT) is a risk factor for visual field loss development among patients diagnosed with preperimetric glaucomatous optic neuropathy (GON). DESIGN: Observational cohort study. METHODS: The study included 98 eyes of 98 patients with GON, with a mean follow-up time of 4.3 +/- 2.7 years. Diagnosis of GON was based on masked assessment of optic disk stereophotographs. All patients had normal standard automated perimetry visual fields at baseline. Criteria for visual field abnormality were derived from a prior study. Several clinical factors (CCT, intraocular pressure, vertical cup-to-disk ratio, refraction, age, gender, family history of glaucoma, high blood pressure, cardiovascular disease, and migraine) were investigated to ascertain whether there is an association with development of repeatable visual field loss. Cox proportional hazards models were used to obtain hazard ratios (HR) and identify factors that predicted which individuals developed glaucomatous visual field loss during the follow-up period. RESULTS: Thirty-four patients (35%) developed repeatable visual field abnormality during follow-up. In multivariate analysis, risk factors that predicted the development of visual field loss were a thinner CCT (adjusted HR = 1.62/40 microm thinner; P =.023; 95% confidence interval [CI]: 1.07-2.45), higher baseline intraocular pressure (adjusted HR = 1.07/mm Hg; P =.022; 95% CI: 1.01-1.14), and larger baseline vertical cup-to-disk ratio (adjusted HR = 1.63/0.1 larger; P =.009; 95% CI: 1.13-2.35). The mean +/- standard deviation CCT of GON patients who developed visual field loss was 543 +/- 36 microm compared with 565 +/- 35 microm of those who did not develop visual field abnormalities (P =.005, Student t test). CONCLUSIONS: Central corneal thickness is a risk factor for development of visual field loss among patients diagnosed with preperimetric GON. It is important to consider CCT when establishing target intraocular pressure of patients with GON.     

Corneal endothelial changes in diabetic dogs

The corneal endothelium of alloxan diabetic dogs was examined by wide-field specular microscopy and compared to that of age-matched non-diabetic dogs. Computer-assisted morphometry of individual cells showed that the diabetic dog endothelium had marked polymegethism and pleomorphism similar to that previously described in diabetic patients. There also appeared to be a positive correlation between the degree of these endothelial changes and the diabetic control as demonstrated by HbA1 concentration.