近视的药物治疗及手术治疗研究进展

近视是最常见的眼病之一,近年来,由于近视的发病率逐年上升,已成为世界性医学问题,近视眼的治疗也成为研究重点。药物研究和手术治疗是近视的治疗目前的研究热点,并已经取得一定得成果。药物方面,阿托品,托品酰胺,哌仑西平,消旋山莨菪碱对近视的控制作用都有被证实,但由于应用上还有一定的副作用,远期效果也不明确,需要进一步研究。手术方面,近视眼手术主要分为角膜屈光手术和眼内屈光手术。LASIK手术是目前应用最广泛的角膜屈光手术方法,SBK手术,飞秒激光手术等技术也日趋成熟。但是,角膜手术存在着一定的风险,应用范围也较为局限,需要进一步研究。眼内屈光手术主要为有晶体眼的人工晶体植入术(PIOL)和屈光性晶状体置换术,矫正的范围更加大,但是眼内手术并发症较多,也需要进一步研究和改进。     

调整非球面因子的近视矫正模型及仿真

针对人眼角膜形状的非球面性,给出了以非球面因子为参数的二次曲面来对角膜表面建模,以此推导了近视矫正量公式,给出各参数的确定方法。与球面假设的近视模型比较,在相同术区大小和矫正近视度数的情况下,非球面假设的近视矫正模型可减小角膜最大切削深度。本模型保证了正常角膜的非球性,理论上可减少术后球差,改善术后视觉质量;本模型可用于指导单纯近视的矫正。     

角膜内皮细胞的检测、受损因素及治疗新进展

摘要：角膜内皮细胞(corneal endothelial cells,CECs)通过其屏障作用及离子泵功能维持角膜透明,但年龄、疾病及创伤等因素会使其功能有所降低,导致角膜失代偿、角膜水肿、大泡性角膜病变,甚至视力的丧失。因此,CECs可谓是角膜的"生命"。近年来,CECs的检测方法逐渐新增,并且不同检测指标具有不同意义;导致CECs受损的因素也有所增加,同时CECs损伤后的治疗也逐渐成为近年来的研究热点。早期发现CECs受损、明确病因并进行干预或治疗会减少CECs的损伤,对指导临床工作有重要的意义。本文主要对CECs检测方法及指标、损伤因素及其治疗的最新进展进行了综述。     

角膜生物力学的测量及临床应用进展

摘要：角膜是重要的屈光间质,约占眼光学系统总屈光力的70％;因其特殊的生理结构,可表现出复杂的生物力学性质。随着近年来科学技术的进步,用于测量角膜生物力学的方法也在不断更新,获得的生物力学参数也更加精确。越来越多的国内外研究团队将对角膜生物力学的研究同临床相结合,发现当角膜形态发生变化时,其生物力学参数也会发生相应的改变。因此,可以通过对患者角膜生物力学的测量来判断病变的发展程度,也可以根据所测得的力学参数来进行手术设计,甚至可以初判患者的愈后情况。但在角膜生物力学方面的研究仍缺乏深度,对其与部分临床疾病的联系仍缺乏充分的认知,仍需探讨如何将角膜生物力学检查更好地服务于临床。本文将对角膜生物力学的离体、活体测量方法及其目前在圆锥角膜、青光眼、翼状胬肉、屈光不正及屈光不正的矫正等临床方面的应用研究作一综述。     

角膜屈光手术后屈光回退的手术治疗进展*

屈光回退是角膜屈光手术后的并发症之一,其治疗方法主要为药物治疗和手术治疗。对于需要再次手术的患者,应根据初次手术方式、距离初次手术时间、回退度数,在充分评价角膜情况后合理选择增效术,确保手术的安全性和有效性。目前,准分子激光原位角膜磨镶术和飞秒激光小切口角膜基质透镜取出术是治疗近视和近视散光的主要手术方式。本文就两者术后屈光回退手术治疗的适应症、不同增效术的优缺点及注意事项作一综述。     

新型准分子激光角膜屈光矫正系统

小光斑高速飞点扫描的准分子激光系统以其具有的治疗时间短、矫正精度高、角膜切削表面极其光滑,易于集成波前像差技术实现“个体化切削”方案等优点,成为眼科屈光矫正激光手术发展趋势。本文从理论基础、光学系统等方面综述了具有自主知识产权的飞点扫描式激光系统,此系统已经在临床动物实验和盲眼实验中取得了非常好的效果。     

兔角膜缘干细胞的研究进展

目前,角膜移植是临床上治疗角膜疾患的最有效途径,但供体角膜非常有限。新近兴起的干细胞技术,为组织工程角膜的研制和应用提供了契机。对于以角膜缘干细胞缺乏或功能障碍为特征的疾病也有治疗效果。采取角膜缘干细胞移植应是一种合理有效的治疗手段。本文主要介绍了兔角膜缘干细胞的体外分离、培养、鉴定及一些生长因子对其增殖的影响。     

框架眼镜联合角膜塑形镜矫正青少年高度近视的临床疗效及对角膜内皮细胞和泪膜的影响

目的:探讨框架眼镜联合角膜塑形镜矫正青少年高度近视的临床疗效及对角膜内皮细胞和泪膜的影响。方法:选取2018年1月2019年3月期间我院收治的青少年高度近视患者98例(181眼),根据信封抽签法分为对照组49例92眼(框架眼镜配戴治疗)和观察组49例89眼(对照组基础上联合角膜塑形镜治疗)。对比两组裸眼视力、屈光度、眼轴长度、角膜内皮细胞密度和数量、泪膜情况以及并发症发生情况。结果:观察组治疗后1个月、3个月、6个月、1年屈光度呈下降趋势(P<0.05),眼轴长度未见明显变化(P>0.05),治疗后6个月、1年裸眼视力较治疗前,治疗后1个月、3个月增加且治疗后1年裸眼视力高于治疗后6个月(P<0.05);观察组治疗后1个月、3个月、6个月、1年屈光度低于对照组(P<0.05),治疗后6个月、1年裸眼视力高于对照组,眼轴长度短于对照组(P<0.05)。两组治疗前、治疗后1年角膜内皮细胞密度(ECD)、六角形细胞(HEX)百分比和细胞面积变异系数(CV)组间及组内对比无差异(P>0.05)。观察组治疗后1年泪膜破裂时间(TBUT)、非接触性泪膜破裂时间(NTBUT)较治疗前下降,且低于对照组(P<0.05)。两组治疗前、治疗后1年基础泪液分泌量(Schirmer)组间及组内对比无差异(P>0.05)。两组并发症总发生率对比无差异(P>0.05)。结论:青少年高度近视的患者在佩戴框架眼镜基础上应用角膜塑形镜,可有效矫正近视屈光度,提高患者裸眼视力,对角膜内皮细胞无明显影响,且不增加并发症发生率,但对人体泪膜稳定性有一定的影响,临床治疗中应加强泪膜情况的戴镜前检查和戴镜后随访。     

组织工程角膜的基础研究和临床应用现状

近年来,组织工程角膜,尤其是组织工程角膜上皮和基质方面的研究取得了很大进展,在动物水平或临床应用中也取得了较好的治疗效果,但在标准化、眼表严重损伤的治疗效果和远期治疗评价等方面仍有一些重大科学问题尚未解决。本文对组织工程角膜的基础研究和临床应用情况进行介绍,并对存在的问题进行了讨论。     

HMGB1在角膜损伤和修复中的作用研究进展

角膜是眼部抵御外来病原微生物侵入的重要屏障,其完整性与眼部健康密切相关。角膜发生损伤后,其自身会进行修复和重新上皮化,该过程常伴随炎症反应及炎症介质的释放。适度的炎症反应可促进损伤修复,而过度炎症反应会伴有大量炎症介质的释放,加剧角膜损伤。高迁移率族蛋白1 (high mobility group box 1, HMGB1)是参与角膜组织损伤和修复过程的常见炎症介质之一,过度表达的HMGB1可加剧角膜修复过程中的瘢痕化,导致角膜透明度降低,对疾病的转归产生负面影响。因此,干扰HMGB1有望成为治疗角膜损伤的新方式。本文从HMGB1的结构与功能、HMGB1在角膜损伤及修复中的作用、HMGB1的调控及其在角膜疾病中的应用三个方面进行回顾和总结。     

Two-photon collagen crosslinking in ex vivo human corneal lenticules induced by near-infrared femtosecond laser

Myopia and keratoconus have become common corneal diseases that threaten the quality of human vision, and keratoconus is one of the most common indications for corneal transplantation worldwide. Collagen crosslinking (CXL) using riboflavin and ultraviolet A (UVA) light is an effective approach for treating ophthalmic disorders and has been shown clinically not only to arrest further progression of keratoconus but also to improve refractive power for cornea. However, CXL surgery irradiated by UVA has various potential risks such as surface damage and endothelial cell damage. Here, near-infrared femtosecond laser-based two-photon CXL was first applied to ex vivo human corneal stroma, operating at low photon energy with high precision and stability. After two-photon CXL, the corneal stiffness can be enhanced by 300% without significantly reducing corneal transparency. These findings illustrate the optimized direction that depositing high pulses energy in corneal focal volume (not exceeding damage threshold), and pave the way to 3D CXL of in vivo human cornea with higher safety, precision, and efficacy.     

Protective Effects of Soluble Collagen during Ultraviolet-A Crosslinking on Enzyme-Mediated Corneal Ectatic Models

Collagen crosslinking is a relatively new treatment for structural disorders of corneal ectasia, such as keratoconus. However, there is a lack of animal models of keratoconus, which has been an obstacle for carefully analyzing the mechanisms of crosslinking and evaluating new therapies. In this study, we treated rabbit eyes with collagenase and chondroitinase enzymes to generate ex vivo corneal ectatic models that simulate the structural disorder of keratoconus. The models were then used to evaluate the protective effect of soluble collagen in the UVA crosslinking system. After enzyme treatment, the eyes were exposed to riboflavin/UVA crosslinking with and without soluble type I collagen. Corneal morphology, collagen ultrastructure, and thermal stability were evaluated before and after crosslinking. Enzyme treatments resulted in corneal curvature changes, collagen ultrastructural damage, decreased swelling resistance and thermal stability, which are similar to what is observed in keratoconus eyes. UVA crosslinking restored swelling resistance and thermal stability, but ultrastructural damage were found in the crosslinked ectatic corneas. Adding soluble collagen during crosslinking provided ultrastructural protection and further enhanced the swelling resistance. Therefore, UVA crosslinking on the ectatic model mimicked typical clinical treatment for keratoconus, suggesting that this model replicates aspects of human keratoconus and could be used for investigating experimental therapies and treatments prior to translation.     

Noninvasive detection of nanoscale structural changes in cornea associated with cross‐linking treatment

Corneal cross‐linking (CXL) using ultraviolet‐A (UVA) irradiation with a riboflavin photosensitizer has grown from an interesting concept to a practical clinical treatment for corneal ectatic diseases globally, such as keratoconus. To characterize the corneal structural changes, existing methods such as X‐ray microscopy, transmission electron microscopy, histology and optical coherence tomography (OCT) have been used. However, these methods have various drawbacks such as invasive detection, the impossibility for in vivo measurement, or limited resolution and sensitivity to structural alterations. Here, we report the application of oversampling nanosensitive OCT for probing the corneal structural alterations. The results indicate that the spatial period increases slightly after 30 minutes riboflavin instillation but decreases significantly after 30 minutes UVA irradiation following the Dresden protocol. The proposed noninvasive method can be implemented using existing OCT systems, without any additional components, for detecting nanoscale changes with the potential to assist diagnostic assessment during CXL treatment, and possibly to be a real‐time monitoring tool in clinics.     

Partial Contact Indentation Tonometry for Measurement of Corneal Properties-Independent Intraocular Pressure

Inter-individual differences in corneal properties are ignored in existing methods for measuring intraocular pressure IOP, a primary parameter used in screening and monitoring of glaucoma. The differences in the corneal stiffness between individuals can be more than double and this difference would lead to IOP measurement errors up to 10 mmHg. In this study, an instrumented partial-contact indentation measurement and analysis method that can account for inter-individual corneal difference in stiffness is developed. The method was tested on 12 porcine eyes ex vivo and 7 rabbit eyes in vivo, and the results were compared to the controlled IOPs to determine the method's validity. Analyses showed that without corneal stiffness correction, up to 10 mmHg of measurement error was found between the existing approach and the controlled IOP. With the instrumented indentation and analysis method, less than 2 mmHg of differences were founded between the measured IOP and the controlled IOP. These results showed that instrumented partial-contact indentation can effectively account for inter-individual corneal variations in IOP measurement.     

Hereditary keratoconus-like keratopathy in Japanese wild mice mapped to mouse Chromosome 13

Human keratoconus is a common corneal disease with non-inflammatory corneal ectasia, and a subset of this disease is heritable. In an effort to establish animal models for this disease, we discovered Japanese keratoconus (JKC) mice among Mishima molosinus (MSM) mice, an inbred strain of Japanese wild mice (Mus musculus molossinus). Typical phenotypic corneas of JKC mice are, like human keratoconus, conical in shape, although the corneas were often associated with a red punctum at the tip. In contrast to human keratoconus, histological examination revealed the inflammatory changes such as infiltration of capillaries and hematocytes in JKC mouse corneas. Although JKC mouse corneal change is probably secondary to keratitis and is a mouse-specific keratopathy, its pathogenesis may be relevant to that of human keratoconus. Linkage analysis mapped the responsible gene at the markers D13Mit21, D13Mit252, D13Mit279, and D13Mit39, which are located between 21.9 and 34.0 cm of the mouse Chr 13. Candidate genes in this region include genes for cathepsins, interleukin, and chemotaxin. Further study of JKC mice may shed light on pathogenesis of human keratoconus.     

高通量测序数据的基因组拷贝数变异检测方法综述

拷贝数变异是指基因组中发生大片段的DNA序列的拷贝数增加或者减少。根据现有的研究可知,拷贝数变异是多种人类疾病的成因,与其发生与发展机制密切相关。高通量测序技术的出现为拷贝数变异检测提供了技术支持,在人类疾病研究、临床诊疗等领域,高通量测序技术已经成为主流的拷贝数变异检测技术。虽然不断有新的基于高通量测序技术的算法和软件被人们开发出来,但是准确率仍然不理想。本文全面地综述基于高通量测序数据的拷贝数变异检测方法,包括基于reads深度的方法、基于双末端映射的方法、基于拆分read的方法、基于从头拼接的方法以及基于上述4种方法的组合方法,深入探讨了每类不同方法的原理,代表性的软件工具以及每类方法适用的数据以及优缺点等,并展望未来的发展方向。     

Riboflavin/UVA collagen cross-linking-induced changes in normal and keratoconus corneal stroma

Purpose

To determine the effect of Ultraviolet-A collagen cross-linking with hypo-osmolar and iso-osmolar riboflavin solutions on stromal collagen ultrastructure in normal and keratoconus ex vivo human corneas.

Methods

Using small-angle X-ray scattering, measurements of collagen D-periodicity, fibril diameter and interfibrillar spacing were made at 1 mm intervals across six normal post-mortem corneas (two above physiological hydration (swollen) and four below (unswollen)) and two post-transplant keratoconus corneal buttons (one swollen; one unswollen), before and after hypo-osmolar cross-linking. The same parameters were measured in three other unswollen normal corneas before and after iso-osmolar cross-linking and in three pairs of swollen normal corneas, in which only the left was cross-linked (with iso-osmolar riboflavin).

Results

Hypo-osmolar cross-linking resulted in an increase in corneal hydration in all corneas. In the keratoconus corneas and unswollen normal corneas, this was accompanied by an increase in collagen interfibrillar spacing (p<0.001); an increase in fibril diameter was also seen in two out of four unswollen normal corneas and one unswollen keratoconus cornea (p<0.001). Iso-osmolar cross-linking resulted in a decrease in tissue hydration in the swollen normal corneas only. Although there was no consistent treatment-induced change in hydration in the unswollen normal samples, iso-osmolar cross-linking of these corneas did result in a compaction of collagen fibrils and a reduced fibril diameter (p<0.001); these changes were not seen in the swollen normal corneas. Collagen D-periodicity was not affected by either treatment.

Conclusion

The observed structural changes following Ultraviolet-A cross-linking with hypo-osmolar or iso-osmolar riboflavin solutions are more likely a consequence of treatment-induced changes in tissue hydration rather than cross-linking.     

紫外光-核黄素交联法对豚鼠巩膜生物力学特性的影响

目的探索紫外光-核黄素交联法对巩膜织张力和强度的影响。方法交联组和对照组皆选右眼为实验眼,交联组采用波长为（370±5）nm、辐射强度定为3.0 mW/cm2的紫外线和0.1%核黄素为光敏剂对豚鼠赤道部巩膜面进行胶原交联,对照组不进行交联处理。术后一个月取交联组交联区巩膜条带和对照组相应区域的巩膜条带,进行生物力学测试,并对眼球各组织进行HE染色光镜和透射电镜检测。结果交联组巩膜的生物力学特性增强,赤道部交联组巩膜试件断裂时的极限应力增加了147%,弹性模量显著增加了193%,极限应变降低了21.9%;后极部交联组巩膜试件断裂时的极限应力增加了108%,弹性模量显著增加了191%,极限应变降低了40.42%。HE染色光镜检查结果显示形态学无病理改变,透射电镜结果显示交联组交联区的巩膜成纤维细胞增生活跃。结论紫外光—核黄素交联法可以有效地提高巩膜的生物力学特性,增强巩膜组织的张力和强度,有望作为治疗高度病理性近视的一种方法。