Congenital cranial dysinnervation disorders

Congenital cranial dysinnervation disorders (CCDDs) are responsible for 1-2% of infant strabismus cases. Insufficient innervation and misinnervation of aberrant nerve fibres lead to motility restrictions and synkinesis. We present the most common CCDDs and explain their pathogenesis and the resulting clinical features. Furthermore, we emphasize essential diagnostic steps and treatment aspects.     

The Genetic Basis of Incomitant Strabismus: Consolidation of the Current Knowledge of the Genetic Foundations of Disease

Abstract

In recent years, our understanding of the genetic foundations of incomitant strabismus has grown significantly. Much new understanding has been gleaned since the concept of congenital cranial dysinnervation disorders (CCDDs) was introduced in 2002, and the genetic basis of CCDDs continues to be elucidated. In this review, we aim to provide an update of the genetic and clinical presentation of these disorders. Disorders reviewed include Duane syndrome (DS), HOXA1 and HOXB1 syndromes, Moebius syndrome, congenital fibrosis of the extraocular muscles (CFEOM), and horizontal gaze palsy with progressive scoliosis (HGPPS).     

Congenital cranial dysinnervation disorders

The European Neuromuscular Centre (ENMC) derived the term Congenital Cranial Dysinnervation Disorders in 2002 at an international workshop for a group of congenital neuromuscular diseases. CCDDs are congenital, non-progressive ophthalmoplegia with restriction of globe movement in one or more fields of gaze. This group of sporadic and familial strabismus syndromes was initially referred to as the 'congenital fibrosis syndromes' because it was assumed that the primary pathologic process starts in the muscles of eye motility. Over the last few decades, evidence has accumulated to support that the primary pathologic process of these disorders is neuropathic rather than myopathic. This is believed that for normal development of extra ocular muscles and for preservation of muscle fiber anatomy, normal intra-uterine development of the innervation to these muscles is essential. Congenital dysinnervation to these EOMs can lead to abnormal muscle structure depending upon the stage and the extent of such innervational defects. Over last few years new genes responsible for CCDD have been identified, permitting a better understanding of associated phenotypes, which can further lead to better classification of these disorders. Introduction of high-resolution MRI has led to detailed study of cranial nerves courses and muscles supplied by them. Thus, due to better understanding of pathophysiology and genetics of CCDDs, various treatment modalities can be developed to ensure good ocular alignment and better quality of life for patients suffering from the same.     

先天性颅神经异常支配性疾病及分子遗传学研究进展

先天性颅神经异常支配性疾病（congenital cranial dysinnervation disorders,CCDDs）为先天性、非进行性散发或家族性的颅神经肌肉疾病,其病因为一条或多条颅神经发育异常或完全缺如,从而引起原发或继发的对肌肉的异常支配。可表现为垂直眼球运动异常,水平眼球运动异常和面肌麻痹。以往这类疾病常被称为先天性纤维化综合征,最近的神经病理学、神经影像学和分子遗传学研究表明该类疾病是由于脑干颅神经核和（或）颅神经的发育异常引起。本文对不同类型CCDDs的临床及分子遗传学研究进展作一综述。     

CCDD Phenotype Associated with a Small Chromosome 2 Deletion

Abstract

Purpose: Some individuals are born with congenital limitation of ocular motility, often associated with ptosis and retraction of the globe. Many of these disorders are now known as the congenital cranial dysinnervation disorders (CCDDs). While several genes have been associated with CCDD phenotypes, there are still patients for whom the genetic basis has not been identified. Methods: Clinical evaluation and neuroimaging, sequencing of candidate genes, and array comparative genomic hybridization (array CGH). Results: The patient was a four-year-old girl with mild dysmorphism; bilateral mild ptosis; substantial limitation of abduction OS with milder limitations of abduction OD, adduction OS, and vertical gaze OS; and retraction OS?>?OD on attempted adduction. No mutations were detected in the HOXA1, KIF21A, SALL4, TUBB3, and CHN1 genes. Array CGH revealed a 8 Kb de novo deletion on chromosome 2 (2q24.3) that encompassed a portion of only one gene, the Xin Actin-binding Repeat containing 2 (Gene Symbol XIRP2; NM_001079810). This gene encodes a protein that is involved in muscle development and protecting actin filaments from depolymerization. It interacts functionally with 10 other proteins playing a similar role in muscle development. Conclusions: This patient’s chromosomal abnormality affected only one gene that currently seems involved only in muscle development. All other genes currently associated with the CCDDs affect neurologic development. Genetic information from this patient implies that genes involved in development and maintenance of extraocular muscles can cause congenital ocular motility disorders as well.     

先天性眼外肌纤维化临床特征分析

目的 对住院行手术治疗的先天性眼外肌纤维化(CFEOM)病历进行临床总结,以加深对此病的认识.方法 回顾性病例分析.对40例(75只眼)CFEOM患者的病历资料进行回顾性总结和分析,包括性别、手术年龄、屈光状态、视力、分型、斜视度、眼部和全身合并症、家族史和手术方法.结果 在40例患者中,男26例,女14例,性别比约为2∶1;手术年龄2～36岁;在有屈光记录的60眼中,单纯远视7只眼,占11.67％;单纯近视2只眼,占3.33％;散光51只眼,占85.00％;在有矫正视力记录(不包括高度近视及视神经病变者)的56只眼中,弱视占94.64％.CFEOM 1型29例,占72.5％;CFEOM 3型10例,占25.0％;CFEOM 2型1例,占2.5％.有家族史者10例,占25％.手术方式:根据斜视方向及肌肉纤维化情况选择肌肉后徙、后徙悬吊或断腱减弱及相应结膜后徙术,相应的拮抗肌若被动牵拉试验没有明显限制,可考虑该肌的加强术;62只眼术后斜视改善,3只眼术后斜视无变化,2只眼垂直斜视改善水平斜视过矫.结论 CFEOM属于少见的先天性颅神经支配异常性疾病(CCDDs),在本资料中,散光性屈光不正者比例较大,弱视发生率较高,CFEOM 1型居多,多数患者手术可使斜视明显改善.     

近十年国家自然科学基金对白内障领域资助的分析

目的：分析2010～2019年国家自然科学基金对白内障研究的资助情况,探讨近期白内障基础研究的发展重点,为白内障领域科研人员了解专业基础研究的进展和申请资助提供参考信息。

方法：统计2010～2019年国家自然科学基金对白内障领域研究的资助项目,对获得资助的项目类别、项目名称、经费数额、申请单位和地区、批准年度及关键词等进行统计和分析。

结果：近十年来,白内障研究的项目数及受助金额分别占眼科学总数的9.35%和9.72%。眼科学和白内障研究的项目数量及受助金额总体呈波浪式上升趋势。立项项目中的关键词逐渐增多,且愈发倾向于机制研究。计算机辅助技术、TALEN技术和全外显子测序技术等的发展,使得白内障研究整体呈现出医学与其他学科融合的趋势。华东地区,尤其上海市项目数量及受助经费位居各省市首位。各项目类别中,数量及经费均为面上项目最多,近几年青年科学基金项目数量强势崛起,甚至在某些领域超过面上项目。

结论：2010～2019年白内障研究的热点趋向于多样化,多学科的融合以及新技术新方法的运用为显著特点。资助力度和研究水平呈现地区发展不平衡。     

Proliferative diabetic retinopathy: pathophysiology of extraretinal complications and principles of vitreous surgery

Extraretinal complications of proliferative diabetic retinopathy are caused by neovascular and/or fibrovascular tissue growth and include vitreous hemorrhage, retinal detachment, and other effects damaging the retina and/or optic nerve. Exact features of fibrovascular tissue growth and secondary complications vary widely from case to case. However, the structural pathogenesis of this disease process is consistent because the abnormal tissue nearly always grows along the posterior vitreous surface. Therefore, differing topographic features and secondary complications are dependent on: (1) the places of origin and amount of fibrovascular proliferation, and (2) the location and extent of any posterior vitreous separation. The latter influences the configuration of the fibrovascular tissue growth and determines the effect on the underlying and adjacent retina. Surgical treatment of proliferative diabetic retinopathy is based on this fundamental structural pathophysiology. The -principles of surgery are to minimize damaging effects by reversing the optical and structural complications and preventing recurrence of similar problems. Therefore, the objectives of surgery are to remove any intravitreal opacities and to excise the posterior vitreous surface. To achieve these objectives, various specialized techniques are required, depending on the complexity of the vitreoretinal anatomy in each case. Still, when the objectives are achieved, the operation has similar beneficial immediate and long-term effects in most eyes. This paper discusses and illustrates the structural pathology of proliferative diabetic retinopathy and the principles and methods of surgical therapy, and it presents the results obtained and the complications encountered.     

脉络膜血流灌注与儿童近视的相关性研究进展

近视是最常见的屈光不正类型。目前我国近视低龄化与快速增长特点明显,青少年儿童近视已成为全社会关注的公共卫生问题。视觉经验指导儿童屈光状态与正视化的发育。近视的发生与发展伴随着眼球结构改变,脉络膜呈现变薄趋势。脉络膜的厚度变化可能由血流灌注决定。脉络膜血流灌注下降可能导致巩膜缺血缺氧,缺氧诱导巩膜基质重塑和眼轴增长。本文就脉络膜血流与近视的相关性展开综述,提示关注脉络膜变化在近视防控中的意义。     

近视与脉络膜厚度的相关性

近视是引起视力损害的一个全球性公共问题,它的发生发展常常伴随着眼部各个组织结构的变化,尤其是病理性近视,涉及巩膜、脉络膜及视网膜等退行性变化.近年来,随着近视患病率越来越高,近视病理机制的探索及防治已成为全球性无法忽视的重要问题.近视的发生发展涉及多种因素的参与,最终会造成严重的视觉损害.脉络膜作为眼部重要的血管组织,...     

四川省整合防盲资源开展大规模白内障防盲手术的探讨

目的:探索四川省整合利用各种防盲资源,提高大规模白内障防盲手术项目的效率与质量的方法,推动防盲工作的发展。方法:分析比较2000年以来由卫生与残联各自单独与合作开展大规模白内障防盲复明手术项目效果。结果:四川省卫生与残联合作2004/2006高质高效完成8548例白内障防盲复明手术,取得了显著成果。手术质量与工作效率较卫生、残联各自单独开展有较大提高。结论:以政府为主导协调整合各方防盲资源开展防盲工作,是防盲工作可持续发展的方向。     

A morphologic and morphometric analysis of the aqueous outflow system of the developing cat eye

The cellular and tissue changes accompanying the development and growth of the aqueous outflow system of the cat were investigated by quantitative light microscopy and by scanning and transmission electron microscopy. As in primates, the trabecular beams and sheets of the cat aqueous outflow system developed by reorganization of cells and extracellular matrix within the tissue filling the anterior chamber angle recess. Enlargement and coalescence of intercellular spaces gave rise to intertrabecular channels. From 3 to 9 days after birth, communications were established between the anterior chamber and intertrabecular spaces by perforation and resorption of tissue which initially covered the angle apex and appeared to be a peripheral extension of Descement's membrane and the corneal endothelium. Macrophage-like cells could be involved in this process. A rapid increase in the volume of the intertrabecular spaces and in the number of trabecular cells coincided with the opening of the trabecular meshwork to the anterior chamber. The trabecular meshwork grew 150-fold in volume from birth to adulthood, mainly as a result of a similar-fold expansion of its connective tissue components. The volume of the intertrabecular spaces increased 24-fold and trabecular cell number increased 14-fold during this same period. The disproportionate increase in volume of the various components of the trabecular meshwork was responsible for the decreased cell density and rarefaction displayed by this tissue as development progressed. Development of the aqueous outflow system of the cat is thus a complex, but highly co-ordinated, process, that depends on continued proliferation of cells and extracellular matrix, a progressive ordering of these components, and selective atrophy and removal of specific tissue components.     

屈光参差性弱视同步记录多焦视觉诱发电位和多焦视网膜电图的对比研究

目的探讨弱视发病的可能机制。方法采用VERIS Science^TM4．2多焦电生理系统对24例屈光参差性弱视患者双眼分别进行多焦图形视觉诱发电位(VEP)、视网膜电图(ERG)同步记录和多焦闪光VEP、ERG同步记录,并与30例正常对照的结果进行比较。结果在不同视网膜区域弱视眼多焦图形VEP、ERG反应和多焦闪光VEP、ERG二阶反应振幅均降低,VEP特征峰潜时延长,ERG潜时无改变。弱视眼多焦闪光一阶反应VEP、ERG的反应振幅密度均降低,潜时无明显改变。多焦图形VEP波形异常程度中心区大于周边区,且与弱视眼的视力异常程度有相关性。弱视眼多焦图形和闪光二阶反应的视网膜．皮层传导时间(RCT)显著延长,闪光一阶反应RCT三组无明显差异。结论弱视眼的mVEP和mERG具有明显的特征性改变,表明弱视眼的视网膜、视觉传导通路和视皮层都存在明显损害,且中心区损害重于周边区,中枢损害重于视网膜。(中华眼科杂志,2005,41：41-46)     

糖尿病患者视网膜病变的筛查分析

目的 了解糖尿病(diabetes mellitus,DM)住院患者中糖尿病视网膜病变(diabetic retinopathy,DR)的发生情况,并探讨其相关危险因素.方法 回顾性临床调查研究.对2007年9月至2010年7月期间,在广西医科大学第一附属医院眼科住院的1610例DM患者采用眼底照相方法确立DR诊断,部分患者进行眼底血管荧光造影检查,计算DR发病率,并分析病程、年龄、发病年龄及血压对发病率的影响.结果 1610例(3201只眼)DM患者中DR发病率为30.2%,其中男性为27.3%,女性为35.0%.新确诊的340例DM患者中DR发病率为12.6%.3201只眼中,背景型DR 797只眼,占24.9%,增殖型124只眼,占3.9%.51～60岁年龄组以及在41～50岁间发病的DM患者,DR的发病率最高.45°眼底彩照与FFA检查结果比较,符率为78.1%.结论 以黄斑为中心单视野眼底照像作为早期DR的筛查方法是有效、实用且简便易行的.病程、年龄及发病年龄是DR发病的危险因素,随着病程延长其发病率显著增高.早期对DM 患者进行筛查、定期眼科检查,能及时发现病变、把握治疗时机,降低DR致盲率有着极其重要的意义.

Abstract：

Objective To determine the prevalence of diabetic retinopathy (DR) and to investigate the associated risk factors in patients with diabetes mellitus (DM).Methods Totally 1610 patients diagnosed DM by the WHO diagnostic criteria attending at the First Affiliated Hospital of Guangxi Medical University from 2007 to 2010.The data of disease history, visual acuity, eye disease and intraocular pressure were collected by inquiry and examination.Photography of ocular fundus was used to confirm the diagnosis of DR.According to the criteria of DR, diagnosis and statistics of DR were made and the relationship between the prevalence of DR and duration, age, the age of onset and blood pressure were analyzed.Results The prevalence of DR was 30.2% in 1610 diabetic patients,27.3% for male and 35.0% for female.The prevalence of DR of 340 newly onset diabetes was 12.6%.In 3201 eyes, the incidence of nonproliferative and proliferative DR (PDR) was 24.9% and 3.9%, respectively.The highest prevalence of DR was in the age group of 51 to 60 and the age of onset was 41 to 50 in patients with DM.Compared with FFA, the agreement rate of 45° fudus photography was 78.1%.Conclusions One-field mydriatic digital fudus photography centered at fovea is feasible and handy for screening of early diabetic retinopathy.Age, the age of onset and duration of disease are the risk factors of DR, longer the duration of DM, higher the incidence of DR.For early diagnosis and management of DR, the patient with DM should be examined regularly.It is very important to decrease the rate of blindness of DR.     

Endothelium-derived agents in pericyte function/dysfunction

The major components of blood vessels are the vascular endothelium and its supporting smooth muscle. Significant strides have been made in the understanding of the cellular and molecular biology of these two cell types and in particular their interactions have been the subject of much interest and debate over the past two decades. The vascular endothelium is now known to profoundly influence the synthetic and motor functions of the underlying smooth muscle and participate in the pathogenesis of all the major vascular disorders. Similarly, the vascular smooth muscle has important effects on the overlying endothelium, and any disruption in the cellular physiology of either cell type can result in dysfunction with important effects on blood flow and vascular permeability The majority of this accumulated knowledge relates to the vascular cells of the macrocirculation. Pericytes are the supporting cells of the microvasculature and a body of evidence is now available to show that similar regulatory mechanisms and vessel-wall cross-talk exists between these cells and the microvascular endothelium. Nowhere are these interactions more important than in the retinal microcirculation where autoregulation is vital for the maintenance of smooth and uninterrrupted blood flow. This review focuses on the interactions between retinal microvascular endothelial cells and their associated pericytes and examines the role of the endothelial cell and the pericyte in the pathogenesis of disease.     

波形纤维蛋白在其转基因小鼠晶状体的表达

目的 观察波形纤维蛋白（Ｖｉｍｅｎｔｉｎ）在转基因小鼠晶状体的表达,探讨波形纤维蛋白与内障形成的关系。方法 用显微注射法将鸡的１２．７ｋｂ波形纤维蛋白基因导入小鼠受精卵的雄前核内,经培育、杂交传代得到２０只波形纤维蛋白内障小鼠。取４只白内障眼球及４只正常眼球,制备石蜡切片,采用ＡＢＣ免疫组化方法,观察波形纤维蛋白在晶状体的表达。再分别正常、分部混浊和完全混浊的小鼠晶状体各１只,经ＳＤＳ－聚丙烯酰胺     

儿童眼及视力保健信息化系统的创建与应用

目的：探索儿童眼及视力保健的信息化管理方法,介绍湖州市儿童眼及视力保健信息化系统的创建及应用情况。方法：以《儿童眼及视力保健技术规范》为蓝本,在儿童保健信息管理系统中增加儿童眼及视力保健信息管理模块,并建立数据库,通过市、县、乡三级儿童保健服务网络,实时收集、监测并管理儿童眼及视力保健信息。结果：儿童眼保健信息系统创建后,经在市、县、乡9个适宜技术单位试点应用基础上,逐步以点连线向全市112 个工作站点推广覆盖,录入系统信息4 千条,提高了本地区儿童眼保健服务质量与儿童眼病筛查率,有利于儿童眼保健档案建立,实现对儿童眼病现况的统计、分析。结论：儿童眼及视力保健信息化提高了儿童眼保健管理平,能为决策层决策提供全面的科学依据,是儿童保健事业发展的必然趋势。     

Histological characteristics of ocular structures after YAG-laser exposure of various sections of the crystalline lens in experimental studies]

This work was aimed at analysis of all the aspects, pathomorphologic included, of short-pulsed YAG laser exposure of the lens. Experiments were carried out with 79 rabbit eyes. After laser exposure the eyes were enucleated in 1-24 h and in 7-10 days. Thirty-one eyes were subjected to YAG laser ++capsule puncture. Fragmentation of intracapsular structures was carried out in 23 eyes. Combined operations were performed on 25 eyes. Every series comprised two groups, differing by the energy of laser exposure: 3-5 mJ. Histologic analysis has lead the authors to the following conclusions. The pattern and severity of pathomorphologic changes were directly related to the energy and time of laser exposure and site of the focal plane of irradiation. The major destructive shifts after YAG laser fragmentation of the cortical layer and capsulotomy are focussed at the site of exposure and involve the adjacent sections of the lens. Laser exposure of 3-5 mJ may be used to open the anterior capsule of the lens and to facilitate the cataract mass discharge in extracapsular cataract extraction. Use of combined method helps enhance induration and fragmentation of the cortical layers of the lens, rules out surgical discission of the anterior capsule of the lens, and facilitates removal of the nucleus and wash out of the lens mass.