角膜神经的研究进展

角膜具有丰富的神经末梢,是机体中最敏感的组织之一,对于保持眼表的完整性具有重要作用。业已证实,有许多疾病与角膜神经相关,如角膜炎、干眼征和糖尿病等。本文从角膜神经的起源、研究方法、分布与形态学结构、角膜神经的再生以及相关疾病几个方面对其作一综述。     

兔眼LASIK手术前后角膜表面超微结构变化和角膜神经染色观察

目的观察准分子激光原位角膜磨镶术（LASIK）手术前后角膜上皮超做结构的变化和角膜神经再生情况。方法新西兰白兔48只,分为2组进行实验,每只兔1只眼行常规LASIK,分别在术后即刻、1d、1周,1、3、6个月,每组各取4只角膜,进行透射电镜、扫描电镜分析和角膜神经染色观察。结果透射电镜观察显示：术后兔眼角膜表面的微绒毛不规则,微绒毛密度明显减少;扫描电镜可见细胞间连接异常,微绒毛有水肿和断裂的迹象。在术后1周左右基本恢复正常。角膜上皮微绒毛数量在术前和术后即刻相比差异有统计学意义（P〈0．05）,与术后1d和7d相比差异无统计学意义（P〉0．05）。角膜神经染色显示术后1d,神经损伤边界清楚,神经纤维被截断,至术后1个月即可见再生神经长人切断的角膜瓣内;术后6个月,再生神经长人角膜瓣内近中心区。结论LASIK术后早期角膜上皮超微结构的改变,可能是造成术后干眼症的原因之一。LASIK术后被切断的角膜神经修复是从断端逐渐向角膜瓣内长人。     

Sjoegren综合征和非Sjoegren水液缺乏性干眼患者角膜上皮基底层下神经的异常改变

干眼是常见的眼表疾病，水液缺乏性干眼是其中常见的临床亚型。水液缺乏性干眼分为Sjoegren’s综合征（Sjtigren’ssyndrome，SS）和非SS水液缺乏性（non-Sjoegren’saqueous tear deficiency，NSTD）干眼两种类型。研究发现干眼患者的角膜知觉发生明显改变，表明其神经的功能发生了改变，但目前对于干眼患者角膜神经是否发生形态学改变的研究不多，而且研究结果不一致。为此，我们应用共焦显微镜技术对11例SS和27例NSTD患者的角膜神经进行研究，并与35例正常人角膜进行了对照，现将结果报道如下。     

基于共聚焦显微镜图像拼接方法分析干眼患者角膜神经形态

目的：探讨使用活体共聚焦显微镜（IVCM）角膜神经图像拼接方法分析干眼患者角膜神经形态特点 及其与干眼临床指标的相关性。方法：系列病例研究。收集2021年1─5月于北京大学人民医院眼 科就诊的干眼患者16例（16眼）。所有患者均进行无创伤泪河高度（NITMH）、无创伤泪膜破裂时间 （NITBUT）、荧光素染色泪膜破裂时间（TBUT）、角膜荧光素染色（FL）评分、睑板腺缺失比例、基础 泪液分泌试验（SⅠT）、IVCM等检查。分别使用传统方法和新的拼接图像处理方法分析患者角膜上皮 下神经图像面积、神经总长度、神经密度、平均神经长度、最长神经长度、最短神经长度、神经数量、 神经数量密度等指标。纳入右眼数据进行分析。2种方法间角膜神经分析的数据比较采用wilcoxon 秩和检验。干眼临床指标与角膜神经分析数据的相关性采用Spearman相关性分析。结果：新的拼接 图像分析方法在角膜上皮下神经图像面积、神经总长度、神经密度、平均神经长度、最长神经长度、 神经数量方面均明显大于传统分析方法（均P<0.05）;最短神经长度较传统分析方法短（P<0.001）;神 经数量密度较传统方法比较差异无统计学意义。使用传统分析方法时,NIKBUT与平均神经长度、 神经数量、神经数量密度均有相关性（r=0.52,P=0.037;r=-0.62,P=0.011;r=-0.62,P=0.011）,其 余干眼指标与角膜神经指标均无相关性。而使用拼接图像分析方法时,NIKBUT与平均神经密度呈负相关（r=-0.56,P=0.025）,其余干眼指标与角膜神经指标均无相关性。结论：相比传统分析方法, 新的拼接图像分析方法可获得更大角膜神经分析面积。2种分析方法的角膜神经分析结果不同,部 分干眼指标与角膜神经分析结果的相关性也不同。新的共聚焦显微镜图像拼接分析方法能够更准确、 更可靠地评估干眼患者角膜上皮下神经情况。     

糖尿病角膜神经病变的研究进展

糖尿病周围神经病变是糖尿病的常见并发症之一,在糖尿病患者中的发病率超过50%,其眼部主要表现为糖尿病视网膜病变和糖尿病角膜神经病变。研究发现糖尿病角膜神经病变早于全身其他部位病变,可为糖尿病周围神经病变的早期诊断、风险评估和治疗方案选择提供有效帮助。糖尿病角膜神经病变的神经损伤修复及治疗是目前研究的热点。本文汇总近年国...     

干眼相关角膜上皮损伤的修复

角膜上皮损伤是指由各种原因导致的角膜上皮功能与完整性被破坏,导致角膜上皮细胞层部分或全层缺失。干眼是角膜上皮损伤的常见原因,也是角膜上皮损伤后延迟愈合或不愈合的主要原因。我国研究者强调泪膜稳定性的改变是干眼发病的核心机制,这也提示我们改善泪膜稳定性在干眼及其相关角膜上皮损伤修复中的重要性。目前临床上应用眼表润滑剂补充泪...     

正常人角膜不同位置角膜知觉的测定分析

人类角膜神经分布密集，大多数神经纤维为感觉神经。这些感觉神经对外界的机械、化学和热刺激所作反应的敏感程度即为角膜知觉。以往采用棉丝检测角膜知觉，近年来发明的CohetBonnet角膜知觉计，可使角膜知觉得以量化测定并分析。为探讨正常人角膜不同位置的角膜知觉分布情况，我们应用CohetBonnet角膜知觉计，检测126位自愿者的角膜中央、鼻侧、颞侧、上方及下方的角膜知觉，现将结果报告如下。     

泪液缺乏型干眼的角膜内皮细胞密度及形态学观察

目的了解泪液缺乏型干眼患者的角膜内皮细胞密度和形态的改变。方法应用SP2000P型角膜内皮计对2005年8月至2006年2月于我院门诊就诊的20例(32眼)典型泪液缺乏型干眼患者进行角膜内皮细胞照相,并以23例(36眼)正常人作为对照,对两组角膜内皮细胞密度及形态进行分析和比较。结果泪液缺乏型干眼组的角膜内皮细胞密度为(2605.4±316.9)个/mm2,内皮细胞平均面积为(389.3±47.1)!m2;正常对照组角膜的内皮细胞密度为(2607.9±313.3)个/mm2,内皮细胞平均面积为(388.7±45.3)!m2,两组比较差异无显著性。泪液缺乏型干眼组内皮细胞平均面积变异系数为(37.3±10.1)%,角膜内皮六边形细胞比例为(52.3±8.9)%;正常对照组内皮细胞平均面积变异系数为(35.3±4.7)%,角膜内皮六边形细胞比例为(47.5±10.9)%,两组比较差异无显著性。结论泪液缺乏型干眼患者与正常人相比,角膜内皮细胞密度和形态无明显改变。     

角膜接触镜曲率对空中乘务员干眼的影响

目的：研究配戴定制曲率软性角膜接触镜对空中乘务员干眼的影响情况。
　　方法：将80例160眼南航空中乘务员分为两组：对照组配戴现成博士伦软性角膜接触镜(曲率为8.4)40例80眼;试验组配戴定制角膜曲率博士伦软性角膜接触镜40例80眼。测量试验前后泪膜破裂时间( BUT )、泪液分泌试验( SⅠt)和荧光素染色( FL)作为干眼症评估指标并对结果进行统计分析。
　　结果：BUT、SⅠt平均值缩短量试验组均比对照组较少,有显著统计学意义(P<0.01)。 FL阳性增加数试验组比对照组较少,有统计学意义(P<0.05)。
　　结论：配戴定制曲率软性角膜接触镜较固定曲率现成品更有效预防空中乘务员干眼发生。     

Geographic distribution of corneal staining in symptomatic dry eye

PurposeTo describe the geographic distribution of corneal fluorescein staining across the five corneal zones, among non contact lens wearers who report symptoms of dry eye and determine which corneal zone most frequently exhibited the worst staining.MethodsPrior studies conducted at the Centre for Ocular Research & Education, Canada, were reviewed for inclusion in the analysis. Each study assessed dry eye symptoms using OSDI and also assessed corneal fluorescein staining in five corneal zones. For each subject, the corneal zones were ranked 1–5 according to their relative staining grade, Rank-1 representing the highest grade.ResultsData from 13 studies and 368 subjects were included. The total number of zones assigned Rank-1 (worst) staining was 449 (across 264 subjects). The inferior zone had the most Rank-1 counts of all zones at 193/43%, which involved 52.5% of all subjects. The nasal zone had 77/17% involving 20.9% of subjects, followed by the temporal (69/15.5%, 18.8% subjects) and superior zones (63/14%, 17.1% subjects). The central zone had the lowest count of Rank-1 designations, at only 47/10.5%, involving 12.8% of subjects. Bayesian analysis was used to generate distributions of the credible proportions of subjects likely to present with staining in a single peripheral zone, with or without central zone staining. It illustrated that staining in a peripheral zone without central staining was more credible. The worst single zone staining was most likely to present in the inferior zone (67.9%), followed by the nasal zone (11.3%), the superior zone (9.2%), and the temporal zone (5.6%).ConclusionIn the presence of dry eye symptoms, the inferior zone typically presents the most severe grade of corneal staining, more likely without central zone staining. This knowledge is valuable when developing a strategy to treat dry eye signs, as the inferior corneal zone has the highest grade of staining thus has the potential to exhibit the greatest reduction in staining post-treatment.     

不同角膜瓣位置对准分子激光原位角膜磨镶术后干眼症的影响

目的观察准分子激光原位角膜磨镶术（LASIK）采用不同位置角膜瓣对术后干眼症发生的影响。方法将230例（460只眼）行LASIK的近视患者按角膜瓣蒂位置分为鼻侧和上方两组,分别观察术前、术后1周、1个月、3个月、6个月干眼症状发生率、泪膜破裂时间检查（BUT）、泪液分泌实验（SchirmerⅠ试验）的结果,并进行分析比较。结果术前两组干眼症状发病率、SchirmerⅠ试验和BUT无差异（P〉0.05）。术后1周时两组比较无明显差异（P〉0.05）。术后1个月、3个月时两组比较均有显著差异（P〈0.01）,术后6个月两组结果无明显差异（P〉0.05）。所有眼在术后6个月干眼症状、SchirmerⅠ及BUT基本恢复正常。结论 LASIK术中制作鼻侧瓣蒂的术眼中干眼症的发生比上方瓣蒂少,干眼症的恢复也快。     

The immunoregulatory role of corneal epithelium-derived thrombospondin-1 in dry eye disease

Purpose

In this study, we examine the expression of corneal epithelium-derived thrombospondin-1 (TSP-1) and its immunomodulatory functions in a validated murine model of dry eye disease (DED).

我国干眼流行病学的研究进展

干眼是一种临床常见的慢性眼表疾病.它是由泪膜的质或量以及泪液动力学异常所致的泪膜不稳定和(或)眼表的损害,进而出现眼部不适及视功能障碍的一类疾病.近年来,我国开展了大量较高水平的干眼流行病学调查研究项目,在干眼的流行病学研究上取得了显著成果.本文中笔者就干眼在我国不同地域和人群中流行病学分布的特征和危险因素进行综述.     

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。     

干眼对生活质量影响的相关研究进展

干眼是一种日益严重的公共卫生问题,临床常见的干眼引起的眼部不适包括眼部干涩、视疲劳、眼异物感、烧灼感及畏光等,进一步可导致视觉损害和对比敏感度降低.这些不适很大程度上影响了干眼患者的身体功能、社会功能、心理功能、日常活动及工作生产力等情况.但干眼的视觉障碍对患者生活质量的影响不易量化,本文中笔者结合现有相关文献,对干眼视觉障碍的评估方法 及其对生活质量的影响进行综述.旨在为临床工作提供指导.     

Advances in the diagnosis and treatment of dry eye

The core mechanism of dry eye is the tear film instability. Tear film-oriented diagnosis (TFOD) is a concept to clarify the cause of tear film instability by tear film, and tear film-oriented treatment (TFOT) is a concept to treat dry eye disease by replacing the lacking components of the tear film layer based on the TFOD. In TFOD, the fluorescein breakup pattern of the tear film is important, and the subtype of dry eye can be judged to some extent from the breakup patterns. Current noninvasive devices related to the dynamic analysis of the tear film and visual acuity enabled the diagnosis of dry eye, subtype analysis, and the extent of severity. In Asian countries, secretagogues represent the main treatment in TFOT. Since meibomian gland dysfunction is a factor that greatly affects the tear breakup time, its treatment is also essential in the dry eye treatment strategy. A newly discovered dry eye subtype is the short breakup time-type (BUT) of dry eye. The only abnormal finding in this disease is the short BUT, suggesting a relationship with ocular neuropathic pain and eye strain. Recently, data from many studies have accumulated which show that dry eye is a life-style disease. In addition to the treatment of dry eyes, it is becoming possible to prevent the onset by intervening with the daily habits, diet, exercise and sleep, etc. It has been pointed out that oxidative stress is also involved in the pathology of dry eye, and intervention is being carried out by improving diet and taking supplements. Future research will be needed to link clinical findings to the molecular biological findings in the tear film.     

Pigment Epithelium-derived Factor secreted by corneal epithelial cells regulates dendritic cell maturation in dry eye disease

PurposeIn this study, we quantify Pigment Epithelium-derived Factor (PEDF) secreted by corneal epithelial cells and evaluate its immunomodulatory functions in a murine model of dry eye disease (DED).MethodsWe induced DED in female C57BL/6 mice using a controlled environment chamber for 14 days. We quantified mRNA expression of Serpinf1 gene and PEDF protein synthesis by corneal epithelial cells (CEpCs) using RT-PCR and ELISA. CEpCs from normal or DED mice were cultured with IFNγ-stimulated-dendritic cells (DCs) for 24 h, and expression of MHC-II and CD86 by DCs was determined using flow cytometry. Next, we either added recombinant PEDF (rPEDF) or anti-PEDF antibody to co-culture, and DC expression of the above maturation markers was quantified. Lastly, we treated DED mice with either topical rPEDF, anti-PEDF Ab or murine serum albumin (MSA), and DC maturation, expression of pro-inflammatory cytokines, and DED severity were investigated.ResultsSerpinf1 mRNA expression and PEDF protein production levels by CEpCs were upregulated in DED. CEpCs from DED mice exhibited an enhanced suppressive effect on the expression of MHC-II and CD86 by DCs, compared to normal mice. This effect was abolished by blocking endogenous PEDF with anti-PEDF Ab or enhanced by supplementing with rPEDF. Treatment with anti-PEDF antibody blocked the effect of endogenous-PEDF and increased DC maturation, expression of pro-inflammatory cytokines in conjunctivae, and exacerbated disease severity in DED mice. Conversely, topical rPEDF enhanced the suppressive effect of endogenous PEDF on DC maturation, decreased expression of pro-inflammatory cytokines in conjunctivae, and reduced disease severity.ConclusionsThe results from our study elucidate the role of PEDF in impeding DC maturation, and suppression of ocular surface inflammation, explicating a promising therapeutic potential of PEDF in limiting the corneal epitheliopathy as a consequence of DED.     

阿托品滴眼液制作兔干眼模型的研究

目的探讨阿托品滴眼液制作兔干眼模型优缺点。方法健康新西兰大白兔12只,随机分为两组:正常组、阿托品组,其中正常组2只兔(4只眼)不接受任何处理,正常饲养14 d和30 d后分别处死1只取泪腺、哈氏腺及角膜行光镜检查,阿托品组10只兔(20只眼)双眼滴用1%硫酸阿托品滴眼液。对阿托品组分别于造模前及造模后第1、3、5、7、11、14天,检查角膜荧光素染色、SchirmerⅠ试验。阿托品造模组点药后14 d后处死取泪腺、哈氏腺行光镜检查,取泪腺及角膜行光镜检查。结果阿托品组用药后11 d内角膜荧光素染色评分增加(P<0.05),但用药14 d后角膜荧光素染色与用药前相比,其差异无显著性意义(P>0.05);用药后第3～11天,基础SchirmerⅠ试验值较用药前显著性减少(P<0.05);用药后14 d检查泪腺、哈氏腺的形态与正常组比较无明显差别。结论阿托品滴眼液点眼制作的干眼症模型经济快速,但不能持久。     

准分子激光原位角膜磨镶术术前干眼的临床调查分析

目的调查分析准分子激光原位角膜磨镶术（LASIK）术前干眼的患病情况及临床特征,指导LASIK术前用药。方法采用非干预性、观察性研究的方法。收集2013年9月至2013年10月就诊于广州军区武汉总医院眼科准分子中心拟行近视手术的患者资料,进行干眼症OSDI问卷调查和相关临床检查,包括裂隙灯检查、角膜荧光素染色（FL）、泪膜破裂时间（BUT）检查,并对临床资料进行分析。结果接受调查35例近视患者中有13例诊断为干眼,患病率37.14%（13/35）。干眼患者的不适症状依次为：畏光14例,最为多见,其次分别为眼痛12例、砂粒感10例、视物模糊8例。OSDI问卷评分（11.13±9.33）分,BUT：（4.87±2.31）s。患病率与性别和年龄的关系：女性高于男性,差异具有统计学意义（P=0.042）;大于30岁者明显高于30岁以下者,差异具有统计学意义（P=0.029）。OSDI问卷分级与2013年干眼临床诊疗专家共识在评估干眼组与正常组得知差异无统计学意义（P=0.44）。屈光度数对干眼发病无影响（P=0.079）。结论 LASIK术前干眼患病率高,术前应做常规干眼检查及治疗,利于提高术后患者的舒适度及视觉质量。