增殖性糖尿病视网膜病变患者活体角膜组织学变化的研究

目的探讨增殖性糖尿病视网膜病变（PDR）患者角膜知觉、激光共焦显微镜下角膜上皮、神经纤维及内皮细胞的组织形态学变化。方法采用激光共焦显微镜对2006年6月至11月于玻璃体视网膜科住院的30例增殖性糖尿病视网膜病变患者进行角膜上皮、神经纤维、内皮细胞形态观察,并行角膜知觉检查;与同期白内障中心住院的同年龄30例非糖尿病患者对照。结果PDR患者角膜知觉较对照组明显减退（P〈0.001）。共焦显微镜检查显示,PDR组角膜上皮细胞、内皮细胞密度均低于对照组（P〈0.05）：角膜神经丛的密度明显低于对照组（P〈0.001）;PDR患者角膜神经纤维纤细,走行迂曲,分支减少多呈钝角。结论激光共焦显微镜已成为在活体状态下观察角膜形态的新方法,增殖性糖尿病视网膜病变患者角膜知觉减退与角膜神经纤维数目减少有关。     

共焦显微镜观察2型糖尿病患者角膜神经分布及形态学特征

目的探讨2型糖尿病患者共焦显微镜下的角膜神经分布及形态学特征。方法应用Confoscan3．0共焦显微镜观察59例（65只眼）2型糖尿病患者和26例（26只眼）同年龄对照组白内障手术患者的中央角膜神经分布和形态学特征,依据双目间接检眼镜和荧光素眼底血管造影检查结果,将糖尿病患者分为3组：糖尿病无眼底改变（NDR）组、非增生性糖尿病视网膜病变（NPDR）组、增生性糖尿病视网膜病变（PDR）组,记录并分析患者角膜上皮下神经丛和角膜基质神经图像。结果与对照组相比,2型糖尿病患者角膜上皮下神经丛神经分支密度、神经纤维长度均减少,差异有统计学意义（P〈0．01）,神经纤维的密度仅PDR组明显减少,NPDR组、NDR组减少不明显。角膜基质中形态异常的神经纤维在糖尿病患者中出现的几率也明显高于对照组,两组差异有统计学意义（P〈0．01）。结论共焦显微镜是一种有效、无创的角膜神经检查方法,2型糖尿病患者角膜上皮下神经丛、角膜基质神经均显示形态学异常。（中华膑群杂志,2006,42：896—900）     

2型糖尿病患者眼表改变的临床分析

目的观察2型糖尿病患者角膜知觉、泪液分泌等眼表改变，及激光共焦显微镜下角膜上皮、神经纤维组织形态学变化，探讨2型糖尿病患者角膜病变的可能机制。方法前瞻性病例对照研究。选取2型糖尿病患者108例，依据眼底情况分为无眼底改变（NDR）组[42例（59眼））和增殖性糖尿病性视网膜病变（PDR）组[66例（86眼）1；选取无全身及眼部疾病的健康体检者（性别、年龄匹配）33例作为对照组。对所有研究对象均进行角膜敏感度测定、基础泪液分泌试验，泪膜破裂时间（BUT）、泪膜分析、角膜荧光素染色及激光共焦显微镜检查。分别对相关数据进行单因素方差分析、卡方检验、Spearman等级相关分析。结果NDR组除泪膜分析结果（大于等于Ⅲ级者占32％）与对照组（14％）的差异有统计学意义外（p，0．01），其他观察项目均无统计学意义。PDR患者角膜敏感度为（33．0±12．4）mm，低于对照组的（47．2±9．7）mm（P〈0．01）；泪液分泌量为（11．8±4．2）mm，少于对照组的（15．2±4．3）mm（P〈0．011；BUT值为（7．3±2．5）s，低于对照组的（13．7±4．0）s（P〈0．01）；泪膜脂质层光干涉图像为Ⅲ级及以上者占50％，高于对照组的14％（P〈0．01）；角膜荧光染色阳性者占74％，高于对照组的8％（P〈0．01）；角膜上皮细胞密度为（4407±480）个／mm^2，小于对照组的（4736±313）个／mm^2（P〈0．01）；角膜神经纤维密度为（898±153）Ixm／视野。低于对照组的（1231＋176）txm／视野（P〈0．05）。且随糖尿病患病时间的延长，角膜敏感度下降fr=0．657，P=0．020）、角膜荧光素染色增多（rm=-0．460，P=0．012）、角膜神经纤维密度减少（r=-0．473，P=-0．020）。结论NDR患者角膜会出现轻度改变，应引起注意，需定期检查；PDR患者角膜已发生明显改变．应积极诊治。     

糖尿病患者角膜朗格汉斯细胞与神经纤维病理改变的研究

目的：探讨糖尿病神经病变患者角膜上皮下朗格汉斯细胞（ Langerhans cell,LCs）与神经纤维病理改变的关系,分析其发病机制,并提出免疫机制在此过程中的可能作用。方法：选取60例糖尿病神经病变患者和32例健康对照者,分析角膜神经纤维形态、数量、长度、角膜知觉和LC细胞密度,并分析二者的相关性。结果：糖尿病神经病变患者角膜神经纤维数量和长度、分支数量明显降低,神经纤维弯曲度明显增加。糖尿病神经病变患者角膜中央和周边上皮下的LC密度与正常对照组相比升高（ P＜0．05）。同时相关性分析结果显示：LC密度和神经纤维密度（r＝0．461,P＝0．011）、长度（r＝0．519,P＝0．002）间存在线性相关。同时糖尿病神经病变患者角膜中央的知觉较对照组明显减退（ P＜0．05）。结论：糖尿病神经病变患者角膜下神经纤维明显受损,角膜知觉减退,LC细胞数量增加,提示这种改变可能是免疫机制介导所致。     

三叉神经痛患者眼表表现及角膜神经的共焦显微镜观察

背景三叉神经眼支是角膜的主要感觉神经和营养神经,三叉神经痛是否会影响患侧眼角膜的功能和形态尚未见报道。共焦显微镜是角膜无创性活体检测的主要手段。目的观察和分析三叉神经痛患者角膜的共焦显微镜下表现及角膜神经在共焦显微镜下形态和密度的改变。方法收集就诊于河南省人民医院疼痛科的33例三叉神经痛患者,对所有受检眼应用角膜知觉敏感度测量计测定角膜知觉,并进行泪液分泌功能测定、泪膜破裂时间（BUT）测定和共焦显微镜观察,对侧眼作为对照组。结果三叉神经痛组角膜知觉测试的纤维长度为（54．348±6．793）mm,正常对照组的角膜知觉平均值为（55．217±6．480）him,差异无统计学意义（t=0．641,P=0．528）;三叉神经痛组SchiemerI试验的滤纸浸湿长度平均值为（9．390±6．583）mm,正常对照组为（9．300±5．295）mm,差异无统计学意义（t=0．070,P=0．945）;2组的BUT平均值分别为（6．09±4．177）S和（6．13±4．799）s,差异无统计学意义（t=-0．085,P=0．933）。角膜鼻侧、颞侧、上方、下方和中央区上皮下神经丛密度与对照组比较,差异均无统计学意义（P=0．840、0．459、0．268、0．120、0．607）。共焦显微镜下三叉神经痛组角膜上皮下神经丛神经纤维数量减少、扭曲;角膜基质中神经丛纤细、盘旋、弯曲;正常对照组上皮下神经纤维分布较密集,平行分布;角膜基质中神经纤维笔直走行,较上皮下神经纤维粗大且分支较多。结论共焦显微镜结果显示三叉神经痛患者患侧眼较正常眼角膜神经扭曲,但眼表功能和角膜神经密度计数无明显改变。     

2型糖尿病患者角膜上皮基底膜沉积物的激光共焦显微镜观察

目的 观察2型糖尿病患者角膜上皮基底膜沉积物在激光共焦显微镜下的表现,探讨糖尿病患者出现角膜上皮病变的可能因素.方法 应用激光共焦显微镜对9例(15眼)2型糖尿病患者和年龄、性别匹配的健康对照眼的全角膜进行分区扫描检查,记录角膜上皮层、前弹力层及前基质层的图像,同时行眼前节光学相干断层扫描(OCT)检查,对所有检查资料进行分析.结果 9例(15眼)中,激光共焦显微镜显示8例(11眼)出现角膜上皮基底膜的异常沉积物,部分沉积物周边可见纤细的神经纤维,角膜上皮层下神经纤维异常,神经纤维密度明显低于正常对照眼.眼前节OCT检查发现有4眼的基底膜、前弹力层及前基质层部位有强反射信号.角膜上皮基底膜沉积物与角膜上皮下神经纤维密度间无明显相关性(r=-0.265,P=0.430).结论 2型糖尿病患者角膜上皮基底膜出现异常沉积物,可能是糖基化终末产物(AGEs)在角膜上皮基底膜的沉积,对糖尿病角膜上皮病变及角膜上皮下神经病变有一定的影响.     

2型糖尿病患者角膜基质细胞形态学特征的共焦显微镜观察

目的 探讨2型糖尿病患者在共焦显微镜下角膜基质细胞形态学特征。方法 应用Confoscan3．0共焦显微镜对120例（146眼）2型糖尿病患者和36例（36眼）同年龄对照组的中央角膜进行检查，依据双目间接眼底镜和荧光素眼底血管造影（FFA）检查的结果，将糖尿病患者分为3组：糖尿病无眼底改变（NDR）组、非增生型糖尿病视网膜病变（NPDR）组、增生型糖尿病视网膜病变（PDR）组，记录角膜基质细胞和基质神经的图像，并对其进行分析。结果 与对照组比较，糖尿病各组角膜的中基质细胞密度均较对照组降低，而前基质细胞的密度只在PDR组有明显的减少，后基质细胞在糖尿病视网膜病变组均明显降低。角膜基质中形态异常的神经纤维在糖尿病组中出现的概率也明显高于对照组，两组间有显著统计学意义（，=36．450，P=0．000）。结论 共焦显微镜是一种有效无创的角膜检查方法；2型糖尿病患者角膜基质细胞密度减少，基质细胞、基质神经均存在形态学的异常。     

分泌减少性干眼症角膜共焦显微镜下的形态学改变

目的应用角膜共焦显微镜活体、无创观察分泌减少性干眼症患者的角膜上皮及上皮下神经纤维的形态学改变。方法选择临床确诊为分泌减少性干眼症的患者37例（73眼）。印迹细胞学检查对患眼进行干燥程度分级,应用角膜共焦显微镜观察角膜上皮下神经纤维的形态学改变,及角膜上皮细胞密度定量测定。结果干眼症患者干燥斑处有明显的角膜上皮细胞坏死脱落区,反光极强;细胞问隙明显增宽,局限上皮细胞缺损、排列稀疏。部分患者呈扁平形浅表层角膜上皮细胞缺失。角膜上皮下神经纤维出现分支紊乱、异常走行弯曲,神经纤维不均匀增粗、增生,7眼未见上皮下神经纤维。干燥程度分级≤Ⅱ级者6眼,角膜上皮细胞密度为（629±168）个／mm^2;Ⅲ级者51眼,细胞密度为（615±181）个／mm^2;≥Ⅳ级者16眼,细胞密度（605±108）个／mm^2,分别与正常眼比较,差异均有统计学意义（P〈0．05）。结论分泌减少性干眼症角膜共焦显微镜下呈现角膜上皮细胞密度降低、上皮下神经纤维的特征性异常改变,与干眼症干燥程度密切相关。     

角膜上皮清创联合羊膜覆盖术治疗糖尿病性角膜病变的临床观察

目的观察角膜上皮清创联合羊膜覆盖术治疗糖尿病性角膜病变的疗效。方法研究组15例（15只眼）采用病变角膜上皮清创加羊膜覆盖术,对照组10例（10只眼）给予保守治疗。结果研究组15只眼中治愈14只眼,对照组10只眼中治愈3只眼,两组疗效有显著差异（P〈0．01）。结论角膜上皮清创联合羊膜覆盖可促进角膜上皮增生和移行,有利于角膜上皮与基底膜的粘合。     

准分子激光术后角膜上皮基底膜下神经分布及形态学特征

目的观察准分子激光原位角膜磨镶术（LASIK）和准分子激光上皮下角膜磨镶术（LASEK）术后角膜上皮基底膜下神经分布及形态学特征。方法共焦显微镜观察低、中度近视LASIK及LASEK27例（54眼）,术前、术后1、3、6月的角膜上皮基底膜下神经纤维分布和形态学特征,并测定泪膜破裂时间（BUT）和泪液分泌量（Schirmer I值）。结果LASIK（12例,24眼）与LASEK（15例,30眼）术后角膜上皮基底膜下神经纤维的再生和形态学在各时间点差异均无统计学意义。两组中BUT有统计学意义（P〈0．05）而Schirmer I值无统计学意义（P〉0．05）。结论对于低、中度近视而言,LASIK与LASEK术后角膜上皮基底膜下神经纤维的再生未显示形态学上的差异。     

Ocular surface changes in type II diabetic patients with proliferative diabetic retinopathy

AIM: To detect and analyze the changes on ocular surface and tear function in type II diabetic patients with proliferative diabetic retinopathy (PDR), an advanced stage of diabetic retinopathy (DR), using conventional ophthalmic tests and the high-resolution laser scanning confocal microscopy. METHODS: Fifty-eight patients with type II diabetes were selected. Based on the diagnostic criteria and stage classification of DR, the patients were divided into the non-DR (NDR) group and the PDR group. Thirty-six patients with cataract but no other ocular and systemic disease were included as non-diabetic controls. All the patients were subjected to the conventional clinical tests of corneal sensitivity, Schirmer I Test, and corneal fluorescein staining. The non-invasive tear film break-up time (NIBUT) and tear interferometry were conducted by a Tearscope Plus. The morphology of corneal epithelia and nerve fibers was examined using the high-resolution confocal microscopy. RESULTS: The NDR group exhibited significantly declined corneal sensitivity and Schirmer I test value, as compared to the non-diabetic controls (P< 0.001). The PDR group showed significantly reduced corneal sensitivity, Schirmer I test value, and NIBUT in comparison to the non-diabetic controls (P < 0.001). Corneal fluorescein staining revealed the progressively injured corneal epithelia in the PDR patients. Moreover, significant decrease in the corneal epithelial density and morphological abnormalities in the corneal epithelia and nerve fibers were also observed in the PDR patients. CONCLUSION: Ocular surface changes, including blunted corneal sensitivity, reduced tear secretion, tear film dysfunction, progressive loss of corneal epithelia and degeneration of nerve fibers, are common in type II diabetic patients, particularly in the diabetic patients with PDR. The corneal sensitivity, fluorescein staining scores, and the density of corneal epithelial cells and nerve fibers in the diabetic patients correlate with the duration of diabetes. Therefore, ocular surface of the patients with PDR should be examined regularly by conventional approaches and confocal microscopy to facilitate early diagnosis and treatment of keratopathy.     

Ⅱ型糖尿病患者角膜的共聚焦显微镜观察

目的共聚焦显微镜下观察Ⅱ型糖尿病患者角膜上皮下神经纤维以及角膜各层细胞密度和形态学改变。设计比较性病例系列。研究对象选取确诊为Ⅱ型糖尿病的患者20例(20眼)为病例组和就诊于眼科门诊的无糖尿病的老年性白内障患者20例(20眼)为对照组。方法病例组和对照组均进行角膜共聚焦显微镜检查,对所得的图片和结果进行分析。主要指标角膜上皮下神经纤维密度、角膜上皮基底细胞密度、角膜浅基质细胞密度、角膜中基质细胞密度、角膜深基质细胞密度、角膜内皮细胞密度、内皮细胞的变异系数和六角形百分比。结果糖尿病组与对照组相比,上皮下神经纤维密度明显减少(t=-4.951,P=0.000);角膜浅基质细胞密度、中基质细胞密度和深基质细胞密度均有显著下降(P值均=0.000);角膜内皮细胞变异系数增加(t’=3.652,P=0.001),六角形百分比减少(t=-3.778;P=0.001)。结论共聚焦显微镜下显示Ⅱ型糖尿病患者角膜上皮下神经纤维密度和各层细胞密度下降。     

Corneal innervation and cellular changes after corneal transplantation: an in vivo confocal microscopy study

PURPOSE: Although penetrating keratoplasty is generally considered a successful procedure, transplanted corneal tissue may exhibit abnormal epithelium, decreased sensation, and declining endothelial cell counts after surgery. This study aimed to use in vivo confocal microscopy to correlate corneal microstructure and recovery of the subbasal nerve plexus of the transplanted cornea with indications for, and time from, surgery. METHODS: This was a cross-sectional study comparing corneas from 42 patients after penetrating keratoplasty with those of 30 controls. Subjects were assessed by ophthalmic history and clinical examination, computerized corneal topography, and laser scanning in vivo confocal microscopy. RESULTS: Time from surgery ranged from 1 month to 40 years (mean, 85 +/- 105 months). Significant reductions in epithelial (P < 0.001), keratocyte (P < 0.001), and endothelial (P < 0.001) cell densities were noted in comparison with control corneas. Significant reductions in subbasal nerve fiber density (P < 0.001) and nerve branching (P < 0.001) were also noted. Endothelial cell density decreased with time after surgery (r = -0.472; P = 0.003), and nerve fiber density (r = .328; P = 0.034) increased. Keratoconus as an indication for transplantation was associated with higher subbasal nerve fiber densities (P = 0.003) than other indications for corneal transplantation. Neither nerve fiber nor cell density was correlated with best-corrected visual acuity. CONCLUSIONS: Laser scanning in vivo confocal microscopy highlights profound reductions in cell density at every level of the transplanted cornea and alterations to the subbasal plexus that are still apparent up to 40 years after penetrating keratoplasty.     

Corneal nerve tortuosity in diabetic patients with neuropathy

PURPOSE: Corneal confocal microscopy is a reiterative, rapid, noninvasive in vivo clinical examination technique capable of imaging corneal nerve fibers. Nerve fiber tortuosity may indicate a degenerative and attempted regenerative response of nerve fibers to diabetes. The purpose of this study was to define alterations in the tortuosity of corneal nerve fibers in relation to age, duration of diabetes, glycemic control, and neuropathic severity. METHODS: The cornea and collected images of the subbasal nerve plexus of 18 diabetic patients (stratified into mild, moderate, and severe neuropathic groups using conventional clinical measures of neuropathy) and 18 age-matched nondiabetic control subjects were scanned, and a novel mathematical paradigm was applied to quantify the extent of nerve tortuosity, which was termed the tortuosity coefficient (TC). RESULTS: TC was significantly different between the four clinical groups (F(3) = 12.2, P < 0.001). It was significantly greater in the severe neuropathic group than in control subjects (P < 0.003) and in the mild (P < 0.004) and moderate (P < 0.01) neuropathic groups. TC did not correlate significantly with the age (r = -0.003, P > 0.05), duration of diabetes (r = -0.219, P > 0.05), or hemoglobin A1c (HbA1c; r = 0.155, P > 0.05) of diabetic patients. CONCLUSIONS: Corneal confocal microscopy allows rapid, noninvasive in vivo evaluation of corneal nerve tortuosity. This morphologic abnormality relates to the severity of somatic neuropathy and may reflect an alteration in the degree of degeneration and regeneration in diabetes.     

Correlation of corneal sensation,but not of basal or reflex tear secretion,with the stage of diabetic retinopathy

PURPOSE: To examine the possible relation between corneal sensation or tear secretion and the stage of diabetic retinopathy in diabetic patients.METHODS: Total reflex or basal tear secretion and corneal sensation were determined in 95 patients with type II diabetes mellitus and 58 nondiabetic control subjects. Tear secretion was measured by the Schirmer test and corneal sensation with a Cochet-Bonnet esthesiometer. RESULTS: Corneal sensation and total or reflex tear secretion were significantly reduced in diabetic patients compared with nondiabetic controls. The loss of corneal sensation, but not that of tear secretion, was significantly correlated with stage of diabetic retinopathy in diabetic patients who were diagnosed with no diabetic retinopathy, simple diabetic retinopathy, preproliferative retinopathy, or proliferative retinopathy. CONCLUSION: Both corneal sensation and total or reflex tear secretion are reduced in individuals with diabetes. The decrease in corneal sensation, but not that in each tear secretion, was correlated with the stage of diabetic retinopathy. Given that loss of corneal sensation is a manifestation of diabetic polyneuropathy, these results are consistent with the notion that both diabetic retinopathy and polyneuropathy result from a basement membrane abnormality.     

Comparison of corneal nerve regeneration and sensitivity between LASIK and laser epithelial keratomileusis (LASEK)

PURPOSE: To compare changes in corneal nerve fibers and keratocyte density by confocal microscopy after laser-assisted in situ keratomileusis (LASIK) and laser epithelial keratomileusis (LASEK). DESIGN: Prospective, nonrandomized comparative clinical trial. METHODS: Fifty-six eyes of 28 patients who underwent LASIK and 52 eyes of 26 patients who underwent LASEK were included. Confocal microscopic data of the central cornea, corneal sensitivity, tear film breakup time, and Schirmer values were determined at three and six months after LASIK or LASEK treatment. RESULTS: In the LASIK group, corneal sensitivity was reduced from preoperative levels at six months after surgery. In the LASEK group, however, there was no difference between baseline and six-month postoperative values. The number of subbasal nerve fibers and the keratocyte density were also different in the LASIK and LASEK groups. The regeneration of corneal nerves correlated strongly with the recovery of corneal sensation and keratocyte density in both groups, whereas the tear film breakup time, Schirmer values, and epithelial thickness did not correlate with corneal nerve regeneration in either group. CONCLUSIONS: The greater decrease in the number of subbasal nerve fibers in the LASIK group compared with the LASEK group may relate to the greater decrease in corneal sensitivity. The pattern of corneal nerve regeneration and the recovery of corneal sensation after LASEK did not differ greatly from that after photorefractive keratectomy in previous studies.     

Correlation of diabetic retinopathy and corneal neuropathy using confocal microscopy

Purpose/Aim: To employ corneal confocal microscopy to assess differences in the extent of corneal nerve fiber alterations between diabetic patients classed according to retinopathy status and nondiabetic patients. Materials and Methods: Two hundred seventy-eight corneas of 139 patients with type 2 diabetes mellitus and 94 corneas of 47 age-matched control participants were scanned using corneal confocal microscopy. Images of the subbasal nerve plexus were collected and analyzed for nerve fiber density (NFD), nerve branch density (NBD), nerve fiber length (NFL), and nerve fiber tortuosity (NFT). Diabetic patients were categorized into three groups according to the classification of diabetic retinopathy (DR) proposed in the Early Treatment of Diabetic Retinopathy Study, based on indirect fundoscopy, fundus photography, and fluorescein angiography findings. A separate classification into four groups according to the severity of peripheral diabetic neuropathy (DN) was also used, based on the results of clinical and electrodiagnostic examinations. Results: Average NFD, NBD, and NFL differed significantly according to DR status and were found to be lower, whereas NFT was found to be higher in diabetic patients than control participants. A positive correlation between diabetic corneal neuropathy and peripheral DN was also found. Conclusions: Nerve fiber alterations of the subbasal nerve plexus of diabetic corneas appear to progress in parallel with DR and peripheral DN. Corneal confocal microscopy could possibly represent a promising adjuvant technique for the early diagnosis and assessment of human DN.