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双语推荐：角膜胶原交联

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角膜胶原交联（CXL）技术是一种治疗圆锥角膜、准分子激光术后角膜扩张、难治性角膜溃疡、角膜炎等角膜疾病的有效方法。它通过紫外光A和感光剂核黄素,介导角膜基质内胶原纤维相互交联而提高角膜机械硬度和角膜基质的生物力学稳定性,从而阻止圆锥角膜等角膜扩张性疾病和难治性角膜炎等的发展。本文就紫外光A核黄素介导角膜交联术治疗感染性角膜炎的基本原理、实验和临床研究现状及其相关安全性等问题进行综述。
Corneal collagen cross-linking ( CXL) through UVA-riboflavin photochemistry has been shown to be an effective treatment for keratoconus , keratectasias and refractory infectious corneal ulcer .CXL increases corneal rigidity , im-proves mechanical and biochemical stability of the stroma , and prevents the progression of corneal expansion and corneal ul-cer.The purpose of this paper is to review basic principles , existing evidences from laboratory and clinical studies , and the safety of corneal cross-linking in the treatment of infectious keratitis .

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角膜是眼球重要的结构之一,呈透明状态,约占纤维膜的前1/6。它所含的胶原蛋白排列规则,可以让光线通过,正是因为胶原蛋白特殊的排列方式,才使角膜拥有良好的透明状态。由此可见胶原蛋白对角膜的重要作用,现在本文就胶原蛋白在角膜中的分布、生理功能、角膜交联术后的变化和临床运用、安全性综述如下。
Cornea is one of the important structure for the eye. It is transparent and locats about 1/6 before fiber membrane. Collagen arrangement is orderly and lets the light through. Because of the special arrangement of collagen, it makes transparent state. Thus it can be seen the important role of corneal collagen. Now we reviewed the distribution of collagen, physiological function, changes of corneal collagen cross-linking, clinical use and security as follows.

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背景 研究表明,核黄素联合紫外线A照射产生的交联效果能够提高角膜的抗酶解能力,并且能够抑制多种细菌的生长.目前胶原交联用于治疗圆锥角膜的效果已得到证实,但能否用于治疗细菌性角膜炎国内尚未见相关报道. 目的 评价离子导入角膜胶原交联法单独应用或联合药物治疗兔眼金黄色葡萄球菌性角膜炎的效果.方法 选取40只成年家兔,右眼角膜基质内注射2×109个/ml金黄色葡萄球菌悬液(比浊法)制备金黄色葡萄球菌角膜炎模型,然后采用随机数字表法将实验兔随机分为模型组、加替沙星滴眼液点眼组、核黄素-紫外线角膜胶原交联组和药物+交联治疗组,右眼为实验眼,左眼为空白对照.于造模后24 h行实验眼角膜分泌物涂片进行细菌培养和鉴定,核黄素-紫外线角膜胶原交联组和药物+交联治疗组行离子导入角膜胶原交联治疗;加替沙星滴眼液点眼组和药物+交联治疗组用加替沙星滴眼液点眼,每日7次,连续14 d.治疗前及治疗后每天于裂隙灯显微镜下检查实验眼并进行炎症分级;分别于治疗前和治疗后14d行眼前节光学相干断层扫瞄(AS-OCT)检查,观察实验眼病变区角膜厚度变化;于治疗后14 d摘出实验眼分别行角膜的组织病理学观察和透射电子显微镜超微结构观察.实验动物的使用和喂养按照潍坊医学院实验动物
Background It is determined that riboflavin/ultraviolet A (UVA)-induced corneal collagen crosslinking is able to increase resistance of cornea against enzymatic digestion and has antimicrobial efficacy for various kinds of bacteria in vitro.However,its in vivo study is less now.Objective This study aimed to evaluate the efficacy of iontophoresis-mediated corneal collagen crosslinking combined with or without drugs for Staphylococcus aureus keratitis.Methods Bacterial keratitis models were induced by the interstromaly injection of Staphylococcus aureus suspension with concentration 2× 109/ml in the right eyes of 40 rabbits,and then the rabbits were randomly classified into the model group,gatifloxacin eye drops group,riboflavin/UVA corneal crosslinking group and drugs+ crosslinking group.The smearing of corneal surface was performed for the identification of bacteria 24 hours after injection.Iontophoresis-mediated riboflavin/UVA crosslinking was applied on the eyes of the rib

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目的 探讨角膜胶原交联联合药物治疗感染性角膜疾病的可行性以及临床疗效.方法 回顾性研究.收集自2011年11月至2012年1月于厦门大学附属厦门眼科中心住院治疗的感染性角膜病患者19例(19只眼),在联合用药无效或效果不佳的情况下进行角膜胶原交联,术后观察指标:主观症状、最佳矫正视力、角膜溃疡愈合情况以及共聚焦显微镜检查.结果 术后1周,15例患者病情好转,3例病情稳定,1例病情恶化；术后1个月,13例患者角膜溃疡愈合,5例病情明显好转,1例穿孔；术后2个月,17例患者角膜溃疡愈合,2例角膜溃疡穿孔,所有17例角膜溃疡愈合患者术后平均随访6个月,无复发.手术前、后最佳矫正视力为眼前手动或眼前指数分别为11只眼和4只眼,0.02 ～0.08分别为5和3只眼,0.1 ～0.2者分别为3和5只眼,术后为0.3 ～0.5者为2只眼,0.5以上者4只眼.与术前相比,术后15只眼裸眼视力提高,4只眼不变.结论 角膜胶原交联联合药物治疗可能是治疗感染性角膜疾病的一个重要补充.
Objective To investigate the feasibility and clinical efficacy of corneal collagen crosslinking (CXL) for the treatment of infectious keratitis.Methods Noncomparative interventional case series.19 patients with infectious keratitis admitted to our hospital between November 2011 and January 2012 were recruited into this study,CXL was performed when medications combined proved poor therapeuticeffects.Postoperatively,the graft status,graft clarity,the visual prognosis and postoperative complications were recorded.Results In 15 cases,there was improvement in symptoms one week after operation.3 cases remained stable,while 1 case reported deteriorated function at the same time.One month after operation,Corneal melting was arrested and complete epithelialization was achieved in 13 cases,5 cases experienced significant improvement and 1 patient experienced corneal ulcer perforation.2 month after surgery,patients with healed corneal ulcer increased to 17cases,and 2 cases experienced corneal ulc

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紫外线A-核黄素交联法能显著提高胶原纤维的机械强度,已被用于治疗圆锥角膜等一系列角膜疾病,且有望通过增强巩膜的生物力学强度而成为治疗进行性近视的新方法.随着应用范围的不断扩展,此疗法的安全性也受到广泛关注.本文以核黄素在眼组织内的弥散过程及饱和判定为重点,分别针对交联疗法中核黄素的作用、直接光损伤、光化学损伤、交联法副作用的预防等方面进行阐述.
UVA-riboflavin cross-linking is an effective approach to increase the mechanical and biochemical rigidity of the collagen fiber,which has been used in treating some corneal diseases such as keratoconus,and might become a new treatment modality for strengthening scleral tissue to prevent progressive myopia,so the safety of the new therapy has be paid attention widely.This article focus on the diffusion process and saturation judgment of riboflavin and describes the effect of riboflavin,direct UV damage,photochemical damage and the prevention of side effects in cross-linking therapy.

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圆锥角膜是一种常见的角膜变性疾病,随着角膜屈光手术的广泛开展,圆锥角膜的早期诊断和合理治疗变得更为重要.传统依靠临床表现或角膜地形图变化进行诊断往往已为时过晚且不能阻止病情进展;而目前除角膜地形图外,综合利用三维眼前节分析系统、共聚焦显微镜、生物力学眼反应分析仪、OCT等仪器分析可以在早期筛查出圆锥角膜或疑似病例,通过主动进行角膜胶原交联术等预防性治疗可在早期阻止病情进展.现就目前圆锥角膜的诊断及治疗新进展进行简要评述.
Keratoconus is a common degenerative disorder of the cornea.This article describes new methods for the diagnosis and treatment of keratoconus.Since corneal refractive surgery is widely used,the early diagnosis and rational treatment of keratoconus have become more important.Traditional diagnosis always depends on clinical manifestations and changes in corneal topography but it cannot stop the progression of the disorder.Currently,in addition to corneal topography,a three-dimensional anterior segment analyzer,confocal microscope,ocular response analyzer,OCT and other instruments are being used to screen keratoconus or suspected keratoconus.Active,preventive treatments like corneal collagen cross-linking can stop progression.

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目的 探讨角膜胶原交联治疗中应用低渗性核黄素对较薄型圆锥角膜眼的治疗效果.方法 回顾性研究.收集自2012年6至12月于厦门大学附属厦门眼科中心住院治疗的15例(15只眼)较薄型圆锥角膜患者(去除角膜上皮后角膜厚度＜ 400 μm),角膜胶原交联术中应用低渗性核黄素后再进行紫外线照射.术中观察角膜厚度,术后观察UCVA、BCVA并行角膜地形图检查及角膜内皮细胞计数.对手术前后角膜地形图检查结果及角膜内皮细胞计数的数据进行配对t检验.结果 15只眼术前、术中刮除角膜上皮后、术中使用低渗性核黄素后的平均角膜厚度分别为(399.27±17.87)、(354.00±18.57)、(447.73±20.87) μm.手术前及术后12个月,Kmax分别为(55.73±3.79)、(54.41 ±4.10)D,Kmin分别为(48.39±3.25)、(47.14±2.75)D,手术前后比较差异均有统计学意义(t=4.656,3.782;P＜0.05).部分患者BCVA得到提高.术前及术后12个月角膜内皮细胞计数分别为(2 782.68±274.49)和(2 774.66 ±246.69)个/mm2,两者比较差异无统计学意义(P =0.804).所有手术患者术后无角膜内皮失代偿、角膜瘢痕形成等并发症出现.结论 较薄型圆锥角膜患者术中应用低渗性核黄素可增加手术安全性,疗效稳定.
Objective To evaluate the clinical results of keratoconic eyes with thin corneas that were treated by using corneal collagen cross-linking with hypo-osmolar riboflavin solution.Methods Retrospective,nonrandomized study.Fifteen eyes of 15 patients with progressive keratoconus and corneal thickness of less than 400 μm (without the epithelium) were included in this study.Application of hypoosmolar riboflavin solution to the cornea for 30 minutes after its de-epithelialization was followed by ultraviolet A collagen cross-linking.Corneal thickness was measured with anterior segment OCT before surgery,after epithelial removal,and after hypotonic riboflavin solution application.Before the ultraviolet A application was started,we must be sure that the thinnest cornea was equal to or greater than 400 μm.Examinations comprised an evaluation of uncorrected distance visual acuity and best corrected visual acuity,slit-lamp microscopy,corneal topography,and endothelial cell counting afte

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背景 真菌性角膜溃疡是一种严重威胁视力的炎症性疾病,严重者需行角膜移植术或眼球摘除术.角膜交联术(CXL)是近年来治疗一些角膜疾病的有效方法,但其用于真菌性角膜溃疡的疗效方面少有研究.目的 观察CXL对真菌性角膜溃疡的治疗作用和效果.方法 选取8周龄健康新西兰白兔15只,其中5只作为正常对照组,另取10只兔刮除右侧角膜上皮行角膜划痕,涂抹镰刀菌液,然后行异种脱细胞角膜片覆盖,制备真菌性角膜溃疡动物模型.按照随机数字表法将模型兔随机分为非治疗组和CXL治疗组,每日行裂隙灯显微镜检查,测量角膜病灶的直径,并观察角膜水肿和炎性细胞浸润情况.于CXL治疗后第3、7、14、21、28天分别对非治疗组和CXL治疗组兔眼行眼前节照相和激光扫描共焦显微镜检查.治疗后4周,收集15只实验兔角膜组织,于扫描电子显微镜下检测正常对照组、非治疗组和CXL治疗组角膜胶原纤维的超微结构.结果 实验兔右眼造模后3d即可见角膜病灶区灰白色溃疡灶,激光扫描共焦显微镜下浅基质层局部见豆荚样菌丝.造模后l周角膜溃疡灶加深,范围扩大,激光扫描共焦显微镜下浅基质层见大量真菌孢子和短棒样菌丝,可见角膜内皮细胞层有炎性细胞及前房内渗出.CXL治疗后3、7、14、21 d,CXL治疗组兔角膜上皮缺失范围均小于非治疗组,差异均有统计学意义(P＜0.05).治疗后28 d,正常对照组、非治疗组和CXL治疗组兔角膜胶原纤维束平均直径分别为(24.6±1.8)、(24.9±1.9)和(43.0±7.4)nm,3个组间差异有统计学意义(F=27.05,P=0.00),其中CXL治疗组胶原纤维直径较非治疗组和正常对照组增粗,差异均有统计学意义(t =-5.30、5.40,P＜0.05),胶原纤维间见较多成纤维细胞;而非治疗组兔角膜胶原纤维直径与正常对照组间差异无统计学意义(t=0.25,P＞0.05),正常对照组胶原纤维间少见成纤维细胞.结论 CXL治疗镰刀菌性角膜溃疡疗效显著,安全性好.CXL可使角膜胶原增粗并刺激成纤维细胞增生,抑制真菌生长和炎症反应,加速角膜修复.
Background Fungal corneal ulcer is a visual-threatening eye disease,and drug therapy has a limiting efficacy.Corneal transplantation or eye enucleation sometimes is necessary to the severe patients.Corneal collagen cross-linking (CXL) is an effective method for some corneal diseases,but the study on CXL for fungal corneal ulcer is lack.Objective This study was to evaluate the clinical effectiveness and safety CXL for fungal corneal ulcer.Methods Fifteen 8-week-old healthy New Zealand white rabbits were used in this study and other 5 rabbits served as normal controls.Fungal corneal ulcer models were established in the right eyes of other 10 rabbits by infecting sickle bacteria liquid after corneal scratching and removing corneal epithelium,then decellularized ostrich corneal patch covered the defected cornea.The models were randomly divided into the non-treatment group and the CXL treatment group.Corneal lesions were examined under the slit lamp microscope every day,and cornea was pictu

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角膜病是我国的第二大致盲眼病,目前角膜盲最难解决的瓶颈问题是角膜供体严重不足并缺乏技术推广和培训平台和体系,从事角膜病的专业人才短缺.近5年,我国在角膜病的基础和临床方面的研究已取得较大成绩,尤其在感染性角膜病方面对真菌性角膜炎发病机制和临床治疗研究,已在国际上占有一席之地.此外,在组织工程角膜和脱细胞基质角膜的研究方面,临床研究已取得了较好的初步效果.角膜屈光手术的临床研究几乎和国际先进水平同步,而角膜内皮移植技术在我国还未真正得到普及.人工角膜的临床应用及研制相对落后,仅在极少数单位有限开展;角膜胶原交联术可减缓早期圆锥角膜的发展,在欧洲已被广泛应用于临床,但后两者在我国仍未得到国家管理部门的批准.
In China,corneal disease is currently the second leading cause of blindness.Severe donor shortage,insufficient technique supports and promotion,and the lack of corneal disease specialists due to poor systematic training are all urgent problems to be resolved.The last 5 years have witnessed a considerable progress in basic and clinical researches of corneal disease.Investigations on the pathogenesis and treatment of fungal keratitis have won an international reputation.Results from the study of corneal reconstruction with tissue-engineered and acellular matrix corneas have been tested in clinical trials with good preliminary performance.Moreover,the clinical researches of corneal refractive surgery have kept pace with the latest international progresses.However,Descemet''s membrane endothelial keratoplasty needs further promotion,and the development and application of keratoprosthesis remains a blank.Although keratoprosthesis and corneal collagen cross-linking have been widely

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