结膜松弛症研究进展

流行病学显示结膜松弛症是年龄相关性眼病,老年人常见。球结膜变性、眼球运动及睑板腺功能障碍、下睑缘张力增高、结膜淋巴管受压迫、自身免疫性疾病等可能是结膜松弛症的病因。在结膜松弛症患者泪液中出现调节凋亡相关蛋白质和防御素,黏蛋白减少,泪膜稳定性下降,球结膜杯状细胞减少,并有形态及超微结构异常,松弛结膜影响泪河、泪膜及泪液排泄。结膜松弛症发病机制研究发现泪液中IL-1β、IL-6、肿瘤坏死因子-α等炎性因子增加,使结膜成纤维细胞中MMP-1,3,9过度表达,MMPs与TIMPs之间失去平衡,可能使胶原纤维融解,弹力纤维变性减少,导致球结膜基质和球筋膜囊过度降解,引起眼表泪液异常的病理循环,而发生结膜松弛症。结膜松弛症治疗采用中医辨证施治,纤维蛋白胶应用于结膜松弛症手术治疗中,结膜双极电凝术、半月皱襞切除术及上方结膜松弛症手术治疗术取得临床疗效,并在结膜新月形切除术中应用结膜定量定位切除的方法减少并发症。     

结膜松弛症研究进展

流行病学显示结膜松弛症是年龄相关性眼病,老年人常见。球结膜变性、眼球运动及睑板腺功能障碍、下睑缘张力增高、结膜淋巴管受压迫、自身免疫性疾病等可能是结膜松弛症的病因。在结膜松弛症患者泪液中出现调节凋亡相关蛋白质和防御素,黏蛋白减少,泪膜稳定性下降,球结膜杯状细胞减少,并有形态及超微结构异常,松弛结膜影响泪河、泪膜及泪液排泄。结膜松弛症发病机制研究发现泪液中IL 1β、IL 6、肿瘤坏死因子 α等炎性因子增加,使结膜成纤维细胞中MMP 1,3,9过度表达,
MMPs与TIMPs之间失去平衡,可能使胶原纤维融解,弹力纤维变性减少,导致球结膜基质和球筋膜囊过度降解,引起眼表泪液异常的病理循环,而发生结膜松弛症。结膜松弛症治疗采用中医辨证施治,纤维蛋白胶应用于结膜松弛症手术治疗中,结膜双极电凝术、半月皱襞切除术及上方结膜松弛症手术治疗术取得临床疗效,并在结膜新月形切除术中应用结膜定量定位切除的方法减少并发症。     

结膜松弛症诊断治疗技术

结膜松弛症是由于球结膜过度松弛和/或下睑缘张力高,造成松弛球结膜堆积在眼球与下睑缘、内、外眦部之间形成皱褶,引起眼表泪液学异常,并伴有眼部不适等症状的疾病。结膜松弛症多发生于老年人,常主诉眼部干涩、异物感、泪溢。诊断结膜松弛症的关键是裂隙灯检查见松弛的球结膜堆积在眼球与下睑缘、内眦部、外眦部之间。结膜松弛症根据症状和体征在临床上分为四级。结膜松弛症的球结膜组织发生以弹力纤维减少、胶原纤维溶解为主要的组织病理改变,泪液中出现蛋白质及酶的异常表达,泪液排泄出现障碍。结膜成纤维细胞中基质金属蛋白酶MMP-1及MMP-3过度表达,使得MMPs与TIMPs之间失去平衡,可能使胶原纤维溶解,弹力纤维变性,导致球结膜基质和Tenon’s的过度降解,引起眼表泪液学异常的病理循环,而发生结膜松弛症。结膜松弛症眼部刺激症状严重者,可以给予泪液制剂、润滑剂和皮质类固醇或抗组胺等药物。上述方法无效,选择手术治疗:(1)结膜新月形切除术;(2)结膜缝线固定术;(3)结膜切除羊膜移植术;(4)角膜缘结膜梯形切除术;(5)双极电凝治疗术;(6)下睑缘高张力减弱术。上述手术方法对治疗结膜松弛症都有效,但各有缺点,且有不同适应证。     

结膜松弛症手术治疗临床观察

结膜松弛症可由于球结膜过度松弛和／或下睑缘张力高，导致松弛的球结膜堆积在眼球与下睑缘、内外眦部之间而引起眼表泪液学异常。我科采用手术治疗结膜松弛症效果良好，报告如下。     

结膜松弛症泪液功能改变的观察

结膜松弛症(conjunctivochalasis)是由于球结膜过度松弛和(或)下睑张力高,造成松弛球结膜堆积在眼球与下睑缘,内、外眦部之间形成皱褶引起眼表泪液学异常,并伴有眼部不适(如流泪、干涩、异物感等)症状的疾病[1].有学者发现结膜松弛症可引起泪液动力学异常型干眼[2-5],泪液功能的改变在结膜松弛症的发生与发展中可能起一定的作用,但机制尚不明.因此,本研究对结膜松弛症的泪液功能改变进行检测,以探讨结膜松弛症的发病机制.     

结膜松弛症泪液功能改变的观察

结膜松弛症(conjunctivochalasis)是由于球结膜过度松弛和(或)下睑张力高,造成松弛球结膜堆积在眼球与下睑缘,内、外眦部之间形成皱褶引起眼表泪液学异常,并伴有眼部不适(如流泪、干涩、异物感等)症状的疾病[1].有学者发现结膜松弛症可引起泪液动力学异常型干眼[2-5],泪液功能的改变在结膜松弛症的发生与发展中可能起一定的作用,但机制尚不明.因此,本研究对结膜松弛症的泪液功能改变进行检测,以探讨结膜松弛症的发病机制.     

结膜松弛症泪液功能改变的观察

结膜松弛症(conjunctivochalasis)是由于球结膜过度松弛和(或)下睑张力高,造成松弛球结膜堆积在眼球与下睑缘,内、外眦部之间形成皱褶引起眼表泪液学异常,并伴有眼部不适(如流泪、干涩、异物感等)症状的疾病[1].有学者发现结膜松弛症可引起泪液动力学异常型干眼[2-5],泪液功能的改变在结膜松弛症的发生与发展中可能起一定的作用,但机制尚不明.因此,本研究对结膜松弛症的泪液功能改变进行检测,以探讨结膜松弛症的发病机制.     

结膜松弛症泪液功能改变的观察

结膜松弛症(conjunctivochalasis)是由于球结膜过度松弛和(或)下睑张力高,造成松弛球结膜堆积在眼球与下睑缘,内、外眦部之间形成皱褶引起眼表泪液学异常,并伴有眼部不适(如流泪、干涩、异物感等)症状的疾病[1].有学者发现结膜松弛症可引起泪液动力学异常型干眼[2-5],泪液功能的改变在结膜松弛症的发生与发展中可能起一定的作用,但机制尚不明.因此,本研究对结膜松弛症的泪液功能改变进行检测,以探讨结膜松弛症的发病机制.     

结膜松弛症泪液功能改变的观察

结膜松弛症(conjunctivochalasis)是由于球结膜过度松弛和(或)下睑张力高,造成松弛球结膜堆积在眼球与下睑缘,内、外眦部之间形成皱褶引起眼表泪液学异常,并伴有眼部不适(如流泪、干涩、异物感等)症状的疾病[1].有学者发现结膜松弛症可引起泪液动力学异常型干眼[2-5],泪液功能的改变在结膜松弛症的发生与发展中可能起一定的作用,但机制尚不明.因此,本研究对结膜松弛症的泪液功能改变进行检测,以探讨结膜松弛症的发病机制.     

结膜松弛症泪液功能改变的观察

结膜松弛症(conjunctivochalasis)是由于球结膜过度松弛和(或)下睑张力高,造成松弛球结膜堆积在眼球与下睑缘,内、外眦部之间形成皱褶引起眼表泪液学异常,并伴有眼部不适(如流泪、干涩、异物感等)症状的疾病[1].有学者发现结膜松弛症可引起泪液动力学异常型干眼[2-5],泪液功能的改变在结膜松弛症的发生与发展中可能起一定的作用,但机制尚不明.因此,本研究对结膜松弛症的泪液功能改变进行检测,以探讨结膜松弛症的发病机制.     

Tear lysozyme and lactoferrin levels in giant papillary conjunctivitis and vernal conjunctivitis

We measured tear lysozyme by a radial immunodiffusion assay in patients with contact lens induced giant papillary conjunctivitis (GPC) and in patients with vernal conjunctivitis (VC). The VC and GPC patients had normal levels of tear lysozyme when compared to control individuals who did not have eye disease and to normal individuals who wore contact lenses without difficulty. In contrast, the tear concentration of lactoferrin (another important tear protein produced by the lacrimal glands) was reduced both in VC and GPC patients. Normal levels of tear lysozyme in the presence of reduced tear concentrations of lactoferrin may be a unique pattern in these two ocular conditions. The reduced tear levels of lactoferrin are probably not related to lacrimal gland dysfunction but to other factor(s) important in the pathogenesis of these two ocular disorders.     

Secretion of tears in patients with hemifacial spasm

Hemifacial spasm can cause abnormal tear secretion on the affected side. Thirty patients with this disease were examined using the Schirmer's test without topical anesthetic. Twelve of them showed more tear secretion on the affected side than on the unaffected side. The average Schirmer test value was 30.4 +/- 12.3 mm (+/- SD) on the affected side in the patients and 17.4 +/- 10.9 mm (n = 148) in the control subjects (P less than 0.001). Microvascular decompression surgery reduced the hypersecretion of tears. The results suggest that compression of the facial nerve by a blood vessel causes an excitatory stimulus for tear secretion in patients with hemifacial spasm.     

The glycoprotein (mucus) content of tears from normals and dry eye patients

Tears were sampled by two different methods from patients with ocular pemphigoid, Stevens-Johnson's Syndrome and Sjögren's Syndrome, as well as from normals. The tear glycoprotein (mucus) content was determined by measuring hexosamine after hydrolysis. Also hexuronic acid and protein levels were determined, as well as tear flow rate in some instances. The level of glycoprotein (mucus) in tears was markedly reduced in pemphigoid and Stevens-Johnson, diseases which are characterized by early break-up of the tear film and decreased content of mucus-producing conjunctival goblet cells. Mucus has earlier been shown to be necessary for the wetting of epithelium, but it is questionable whether mucus is reduced enough in pemphigoid and Stevens-Johnson to explain tear film instability in these disease entities.     

Quantification of MUC5AC protein in human tears.

PURPOSE: MUC5AC has been identified as a major secretory mucin of conjunctival goblet cells and precorneal tear film. However, no method has been reported to quantify MUC5AC protein in human tears. The objective of this study was to establish a method to measure the amount of MUC5AC in human tears and to correlate the amount of MUC5AC with age, gender, and dry eye diseases. METHODS: A goat antibody was raised to synthetic peptides corresponding to nonglycosylated epitopes of human MUC5AC mucin. This antibody and a horseradish peroxidase-coupled second antibody were used to develop a quantitative immunoassay to measure the MUC5AC concentration of tear samples collected on Schirmer strips. Porcine stomach mucin was used as a standard for the assay. The chemiluminescent MUC5AC signal was digitized and quantified. Tear samples from 19 healthy volunteers and 31 clinically diagnosed dry eye patients were analyzed. RESULTS: MUC5AC concentration in human tears ranged from undetectable to more than 200 microg/mL porcine stomach mucin equivalent. In the healthy population, low, moderate, and high concentrations were found in the tear samples from younger and older persons and from both men and women. The mean MUC5AC content in tears was lower in the dry eye patients than in the age- and gender-matched healthy individuals. CONCLUSIONS: A method was established to quantify MUC5AC in human tear samples obtained on Schirmer strips. There was no correlation between the amount of MUC5AC and age or gender in the healthy population. Dry eye disease patients, however, typically showed reduced concentrations of soluble MUC5AC in the tear film.     

Analysis of tear proteins in Graves' ophthalmopathy by high performance liquid chromatography

Using high performance liquid chromatography, we analyzed tears from 50 patients with Graves' ophthalmopathy and 20 controls. With this technique, tear constituents are separated according to size; a normal tear protein profile consists of five peaks. An increase in one or more peaks was observed in 14 patients (28%) and in none of the controls. No decreased values were observed. No relation was observed between abnormalities of tear composition and the clinical NO SPECS classification. There was a tendency for increased tear protein peaks in those patients with long-standing disease. Most patients with an increase in one or more tear protein levels had normal thyroid function after treatment for hyperthyroidism. Our findings suggested that the inflammatory process in the orbit occurring in Graves' ophthalmopathy also had an effect on the lacrimal gland, which was reflected in the composition of the tears.     

Recent developments on dry eye disease treatment compounds

Dry eye syndrome is a common tears and ocular surface multifactorial disease, described by changes in the ocular surface epithelia related to reduced tears quantity and ocular surface sensitivity, leading to inflammatory reaction. Managing the eye inflammation proved helpful to patients with dry eye disease and current treatment is based on the use of topically applied artificial tear products/lubricants, tear retention management, stimulation of tear secretion and using anti-inflammatory drugs. In this article we revise the corresponding literature and patents assembling the new treatment approaches of novel and future pharmaceutical compounds destined for the dry eye disease treatment. The most frequent categories of compounds presented are secretagogues and anti-inflammatory drugs. These compounds are the research outcome of novel therapeutic strategies designed to reduce key inflammatory pathways and restore healthy tear film.     

The effect of calcium dobesilate on albumin leakage of the conjunctival vessels

Calcium dobesilate significantly reduced the leakage of serum albumin in the tear fluid in patients with chronic inflammatory reactions of the conjunctiva. In the majority of cases reduction of serum albumin concentration in the tear-fluid was treatment related. The marked increase in tear albumin concentration after treatment, found in two cases, was caused by a sharp increase in the inflammatory reaction due to an exacerbation of the underlying disease during the trial period. No relation was found between improvement of symptoms as reported by the patients and alterations in serum albumin concentrations.     

The relations between tear fluid concentrations of lysozyme,tear-specific prealbumin and lactoferrin

A degeneration of the tear gland leads to reduced lysozyme concentrations in the tear fluid. Tear lysozyme concentrations are generally determined by enzymatic methods. Lysozyme determination by radial immunodiffusion has some advantages above the enzymatic assays, and laboratory facilities are not required. The enzymatic properties of lysozyme that favoured its choice as a parameter for tear gland function, influenced to some extent the results of the radial immunodiffusion assay. Therefore we looked among the proteins originating from the lacrimal gland for alternative parameters of tear gland function.In 94 tear samples obtained from a heterogeneous group, ranging from persons with normal lacrimal gland function to severe kerato-conjunctivitis sicca patients, a high degree of correlation was found between lysozyme concentration and that of lactoferrin as well as tear-specific prealbumin. This indicates that the latter two proteins can be used as alternatives for lysozyme in tear gland function tests.     

泪液渗透压与干眼

干眼病是眼科常见的疾病,发病率呈日益升高的趋势.泪液渗透压增高是造成干眼患者眼部不适、眼表面损伤及眼部炎症反应的主要原因之一.随着泪液渗透压检测技术的突破,关于泪液渗透压的研究及应用也越来越多,不同地区正常人及干眼患者的泪液渗透压值屡见报道.本文分析了泪液渗透压研究进展、泪液渗透压值范围及其在干眼诊断及治疗中的应用,并对低渗人工泪液的临床应用进行展望.

Abstract：

Dry eye is a common eye disease, and its incidence rate has been escalating. The increased tear osmolarity is one of the main reasons for complaint, damage and inflammation of dry eye patients. With the breakthrough of testing technology for tear osmolarity, more research and application of tear osmolarity was reported, and papers on tear osmolarity of normal eye and dry eye in different regions were also published. In this article, the progress of the tear osmolarity research, the range of tear osmolarity and its application in diagnosis and therapy of dry eye was introduced, and the prospect for the clinical application of hypotonic artificial tears was also discussed.     

Proteinanalytische Methoden bei der Diagnostik des Sikka-Syndroms

BACKGROUND: The routine clinical diagnosis of sicca syndrome remains difficult; the results of the standard tests, such as the Schirmer test, tear film break-up time and the rose Bengal test, correlate neither with the course of the disease nor with one another. MATERIAL AND METHOD: We introduce two procedures that can be used to differentiate patients with sicca syndrome from healthy individuals on the basis of tear fluid protein patterns. Electrophoretic separation of the tear proteins or measurement by high-performance liquid chromatography (HPLC) was followed by digital image processing and multivariate discriminant analysis. RESULTS: In addition to analysis of tear protein patterns, these methods permit diagnostic classification. Statistical evaluation reveals whether an unidentified sample is to be classified as sicca syndrome or "healthy". Both HPLC analysis and protein electrophoresis detect differences in protein patterns between the tear fluid of healthy individuals and patients with sicca syndrome and point to a diagnosis accordingly. CONCLUSION: Both of the techniques presented - electrophoresis and HPLC - could potentially be used for diagnostic purposes in the detection of sicca syndrome. The HPLC method of tear protein analysis is more reliable, lends itself more readily to automation and achieved greater success rates in the experiments we describe; for these reasons it is the preferred approach.