The genetic basis for adult onset glaucoma: Recent advances and future directions

Glaucoma, a diverse group of eye disorders that results in the degeneration of retinal ganglion cells, is the world's leading cause of irreversible blindness. Apart from age and ancestry, the major risk factor for glaucoma is increased intraocular pressure (IOP). In primary open-angle glaucoma (POAG), the anterior chamber angle is open but there is resistance to aqueous outflow. In primary angle-closure glaucoma (PACG), crowding of the anterior chamber angle due to anatomical alterations impede aqueous drainage through the angle. In exfoliation syndrome and exfoliation glaucoma, deposition of white flaky material throughout the anterior chamber directly interfere with aqueous outflow.Observational studies have established that there is a strong hereditable component for glaucoma onset and progression. Indeed, a succession of genome wide association studies (GWAS) that were centered upon single nucleotide polymorphisms (SNP) have yielded more than a hundred genetic markers associated with glaucoma risk. However, a shortcoming of GWAS studies is the difficulty in identifying the actual effector genes responsible for disease pathogenesis. Building on the foundation laid by GWAS studies, research groups have recently begun to perform whole exome-sequencing to evaluate the contribution of protein-changing, coding sequence genetic variants to glaucoma risk. The adoption of this technology in both large population-based studies as well as family studies are revealing the presence of novel, protein-changing genetic variants that could enrich our understanding of the pathogenesis of glaucoma.This review will cover recent advances in the genetics of primary open-angle glaucoma, primary angle-closure glaucoma and exfoliation glaucoma, which collectively make up the vast majority of all glaucoma cases in the world today. We will discuss how recent advances in research methodology have uncovered new risk genes, and how follow up biological investigations could be undertaken in order to define how the risk encoded by a genetic sequence variant comes into play in patients. We will also hypothesise how data arising from characterising these genetic variants could be utilized to predict glaucoma risk and the manner in which new therapeutic strategies might be informed.     

预测及筛查原发性闭角型青光眼高危人群的研究进展

危险窄房角者若能在急性房角关闭及周边虹膜前粘连形成之前筛查出高度可疑前房角关闭者,可早期阻断发病环节,对防止演变成原发性闭角型青光眼（primaryangleclosureglaucoma,PACG）具有重要意义。PACG的预测及筛查方法中,前房角镜检查、超声生物显微镜、眼前段相干光断层扫描、Scheimpflug照相技术有各自的优缺点。预测及筛查PACG涉及众多的眼球生物学参数测量,最新的研究进展涉及静态参数与动态参数。前者包括前房深度、宽度、体积、面积,房角开放程度参数,虹膜厚度、体积、曲率,晶状体厚度、相对位置、拱高等;后者包括虹膜容积变化测量及葡萄膜渗漏检查等。     

Risk factors of primary angle closure glaucoma

Primary angle closure glaucoma is one of the common diseases causing blindness. The pathogenesis inducing primary angle closure glaucoma has not been entirely clear. Traditionally identified risk factors include shallow anterior chamber, short axial length and thicker lens. Recent studies begin to pay attention to other new risk factors, not only including static anatomical factors, such as anterior chamber volume, iris curvature and lens vault, but also including dynamic changing factors, such as dynamic dilation of iris volume and choroidal effusion. Comprehensive assessment of these risk factors is of great significance for early diagnosis and treatment of angle closure glaucoma. This article briefly reviews research advances in risk factors of primary angle closure glaucoma.     

Mechanisms and treatment of primary angle closure: a review

Angle closure can recur following peripheral iridotomy in up to 58% of cases, due to plateau iris syndrome, lens disproportion or ciliary block. Ciliary block glaucoma is an important differential diagnosis of shallow anterior chamber, angle closure and high intraocular pressure, which may occur spontaneously or following laser or surgery. Some underlying mechanisms of ciliary block glaucoma remain poorly understood but lens-ciliary body apposition and anterior hyaloid changes with increased hydraulic resistance are major pathogenic factors. An understanding of the pathogenic factors facilitates early recognition of ciliary block glaucoma, and aids a logical sequence of intervention. We review the mechanisms of post-iridotomy angle closure and propose a stepwise treatment strategy for these conditions.     

急慢性閉角型青光眼小梁切除後淺前房發生率對比觀察

目的比較急性閉角型青光眼、慢性閉角型青光眼小梁切除術後淺前房的發生情况.方法對410祗實施小梁切除術的原發性閉角型青光眼進行回顧性總結.結果 99祗眼發生淺前房,占總數24.1%,其中急性閉角型青光眼69祗眼,發生率爲22.3%;慢性閉角型青光眼爲30祗眼,發生率爲29.7%.結論淺前房在慢性開角型青光眼中的發生率高于急性閉角型青光眼.     

激光周边虹膜成形术治疗虹膜切除术后暗室俯卧试验阳性的原发性闭角型青光眼

目的　评价激光周边虹膜成形术治疗虹膜切除术后暗室俯卧试验阳性的原发性闭角型青光眼的临床效果。方法　对激光周边虹膜切除术后暗室俯卧试验阳性的 34例 (5 6只眼 )原发性闭角型青光眼 (非眼外引流手术指征 ,前房角粘连 <1/2周前房角范围 )患者行激光周边虹膜成形术。其中急性闭角型青光眼 2 7例 (49只眼 ) ,慢性闭角型青光眼 7例 (7只眼 )。对患者治疗前后的周边前房深度、前房角、眼压、视野及周边虹膜形态进行详细的对比观察 ,并行暗室俯卧试验及散瞳试验检查。患者术后随访 1～ 4年。结果　所有患者治疗后周边前房深度均明显加深 ,静态前房角镜检查小梁网可见范围增宽。随访期间患者未发生高眼压、前房角进行性粘连及视野损害 ,暗室俯卧试验及散瞳试验均阴性。结论　虹膜切除术后暗室俯卧试验阳性的原发性闭角型青光眼的发病机制是当瞳孔散大时 ,异常的周边虹膜组织堵塞小梁网而引起高眼压 ,瞳孔阻滞因素不起主导作用。激光周边虹膜成形术可以明显改变此类青光眼患者 (前房角粘连 <1/2周前房角范围 )的周边虹膜形态 ,从而控制病情进展。     

不同类型急性闭角型青光眼行晶状体超声乳化吸出术后眼压控制率比较

目的比较不同类型急性闭角型青光眼行晶状体超声乳化吸出术后的眼压控制率及其与前房角改变的关系。设计回顾性病例系列。研究对象急性闭角型青光眼合并白内障以晶状体超声乳化治疗病例173例173眼。方法2005年1月,2007年6月,安溪明仁眼科医院的上述患者173例,通过超声生物显微镜（UBM）检查确定其前房角关闭类型为单纯瞳孔阻滞型（52．0％,90／173）、非瞳孔阻滞型（17．9％,31／173）、混合机制型（30．1％,5／173）。行超声乳化白内障吸除联合折叠型人工晶状体植人术,随访48W;通过UBM对比术前、术后前房深度、前房角变化以及眼压变化。主要指标眼压、前房角开放程度、并发症情况。结果手术后8W三种类型急性闭角型青光眼其眼压控制率分别为单纯瞳孔阻滞型88．9％（64／72）、非瞳孔阻滞型52．0％（13／25）、混合机制型83．4％（35／42）,差异有统计学意义（x^2=7．13,P=0．022）;随访48W时分别为54．2％（13／24）、33．3％（3／9）、35．8％（5／14）,差异有统计学意义（x^2=12．56,p=0．003）。手术中及术后并发症发生率与同期单纯白内障超声乳化手术相当。48W时前房角开放率（UBM检查）分别为单纯瞳孔阻滞型66．7％（16／24）、非瞳孔阻滞型33-3％（3／9）、混合机制型33．3％（4／12）。结论急性闭角型青光眼患者行晶状体超声乳化吸出术其眼压控制有效率依次为单纯瞳孔阻滞型、混合机制型、非瞳孔阻滞型;眼压控制率与前房角开放程度有关。     

前房型人工晶体植入术后继发性青光眼

目的 了解前房型人工晶体（ａｎｔｅｒｉｏｒｃｈａｍｂｅｒｉｎｔｒａｏｃｕｌａｒｌｅｎｓ,ＡＣ－ＩＯＬ）植入术后对眼压,房角的影响及继发性青光眼的发生情况。方法 回顾调查６２只眼ＡＣ－ＩＯＬ植入术后,随访期为３个月至７年,平均３１个月,眼部检查着重度的检查,白内障类型以外伤性及老年性为主,手术方式包括眼前段切除术或白内障囊外摘除（ｅｘｔｒａｃａｐｓｕｌａｒｃａｔａｒａｃｔｅｘｔｒａｃｔｉｏｎ,ＥＣＣ     

房角虹膜前粘分离术治疗闭角型青光眼的临床观察

目的探讨房角虹膜前粘连分离术治疗闭角型青光眼的临床效果。方法 9例（9只眼）闭角型青光眼行房角虹膜前粘连分离术,观察术后眼压、房角及并发症的情况。随访时间6周至4个月。结果 9例（9只眼）术前平均眼压（39.44±12.86）mm Hg,至最后1次随访,术后平均眼压（13.33±1.80）mm Hg,与术前相比明显降低,差异有统计学意义（P〈0.01）。超声生物显微镜（UBM）检查示：术后房角大部分或全开放。并发症：3例发生前房出血渗出,逐渐吸收,无浅前房、脉络膜脱离等并发症。结论对于闭角型青光眼,房角虹膜前粘连分离术疗效确切,具有较好的临床应用价值。     

Determination of anterior segment changes with Pentacam after phacoemulsification in eyes with primary angle‐closure glaucoma

Background: To investigate changes of anterior segment morphology in primary angle‐closure glaucoma after phacoemulsification using the Pentacam system. Design: Prospective, interventional study, Zhongshan Hospital of Sun Yat‐sen University. Participants: Eighty‐five eyes from 60 patients with primary angle‐closure glaucoma undergoing phacoemulsification. Methods: Intraocular pressure was measured by Goldmann applanation tonometry. Anterior segment morphology was assessed using the Pentacam camera. Main Outcome Measures: The intraocular pressure, central anterior chamber depth, peripheral anterior chamber depth, anterior chamber volume, pupil diameter and anterior chamber angle preoperative and 3 months postoperative. Results: A total 78 eyes of 55 patients with primary angle‐closure glaucoma were included in the analysis. Thirty‐two eyes (41.0%) had acute primary angle‐closure glaucoma, and 46 eyes (59.0%) had chronic primary angle‐closure glaucoma. In both groups, statistically significant decreases in intraocular pressure and increases in anterior chamber volume, central anterior chamber depth, peripheral anterior chamber depth and anterior chamber angle inferiorly, nasally, temporally and superiorly were observed at 3 months after phacoemulsification (all P < 0.001). Conclusions: Phacoemulsification induces significant changes in anterior segment morphology in primary angle‐closure glaucoma accompanied by a significant fall in intraocular pressure in the short term.     

原发性闭角型青光眼易患者六年随访研究

目的了解原发性闭角型青光眼的自然发展史和危险因素,为原发性闭角型青光眼的筛检提供有益的经验。方法对４０岁以上人群（６５４８人）中筛选出的原发性闭角型青光眼易患者４８５例进行６年随访,随访检查包括视力、前房轴深、周边前房深度、眼压测定和视乳头杯／盘比。高度可疑者再进一步检查。结果４８５例易患者中,发生闭角型青光眼者２０例（４．１％）,其中自然发病者１４例（急性发作期６例,慢性期８例）,早期发现者６例,２８．０％的易患者前房进行性变浅。结论前房深度是闭角型青光眼筛检的一个重要指标,对于闭角型青光眼易患者的筛检及定期随访十分有意义。     

激光周边虹膜成形术治疗原发性闭角型青光眼房角相关结构的超声生物显微镜观察

目的应用超声生物显微镜(ultrasoundbiomicroscopy,UBM)观察激光周边虹膜成形术治疗原发性闭角型青光眼房角结构的变化,进一步做疗效评价。方法对原发性闭角型青光眼经虹膜切除术后暗室俯卧试验阳性的31例38眼行激光周边虹膜成形术治疗,治疗前后均行眼前节裂隙灯显微镜、房角镜及UBM检查,对于治疗后无发作性眼压升高且连续两次暗室俯卧试验阴性的病例,应用0.5%托吡卡胺点眼散瞳后再行上述检查。结果36眼(94.7%)成功治愈。表现为:无青光眼发作、连续两次暗室俯卧试验阴性且散瞳试验均阴性。所有病例经治疗后周边前房深度均明显加深,静态房角镜检查小梁网可见范围增宽。UBM检查显示周边虹膜形态较术前明显变薄而平直,500um处小梁虹膜夹角(TIA500)、250um和500um处前房角开放距离(AOD250、AOD500)均较术前显著增加(p<0.01),周边虹膜厚度(IT1)明显变薄(p<0.01)。术后观察(1～2)年,疗效稳定且未见明显并发症。结论激光周边虹膜成形术可有效的改变周边虹膜形态,增加前房角宽度,防止瞳孔散大所造成的周边虹膜堆积,是治疗虹膜切除术后仍有急性发作或激发试验阳性的原发性闭角型青光眼安全、有效的治疗方法。     

晶状体摘出术治疗原发性闭角型青光眼的研究进展

晶状体的形态和位置改变所引起的浅前房、瞳孔阻滞及房角关闭是诱发原发性闭角型青光眼(PACG)的因素之一.晶状体摘出术可以增加前房深度,解除瞳孔阻滞;而晶状体摘出术联合房角分离术可使关闭的房角重新开放,防止周边房角前粘连.近年来采用晶状体摘出术治疗PACG的研究取得较大进展,而其作用机制的研究、治疗效果的评价及仍然存在的问题等日益受到关注.就PACG的发生和发展与晶状体改变的关系、晶状体摘出术在治疗PACG中的作用、效果及手术的安全性评价等进行综述.     

探讨Nd：YAG激光周边虹膜切除术远期疗效的预测

目的探讨Nd：YAG激光周边虹膜切除术对闭角型青光眼的远期疗效的预测方法。方法对156例（204眼）接受Nd：YAG激光周边虹膜切除术1～5年后的原发性急性闭角型青光眼临床前期、缓解期和原发性慢性闭角型青光眼早期的患眼进行回顾性的多因素分析。其内容包括：手术前后视力、眼压,中央和周边前房深度、前房角形态以及杯盘比值,部分患者还作暗室试验和视野检查。结果204眼术后,30眼（14．7％）1～5年前房角出现新的粘连闭合或原粘连闭合继续扩大,并发生青光眼性的视功能损害。这些失败眼术前都具有前房隐窝浅、虹膜根部附止靠前、虹膜呈爬行性前粘连,或术后周边前房未明显加深,房角未加宽的临床特点。结论正确评估手术前前房角的形态结构和观测手术后周边前房深度的变化是预测激光周边虹膜切除手术远期疗效的方法,是筛选13后会失败的高危眼的两个重要指标。     

Primary lens extraction for glaucoma management: A review article

Recently, primary lens extraction alone gained more acceptance as an alternative surgical approach for glaucoma management. This view was supported by the advances in phacoemulsification and intraocular lenses with greater safety and visual recovery, in addition to a substantial reduction of intraocular pressure and deepening of the anterior chamber and filtration angle. The decrease in IOP after cataract surgery in primary open-angle glaucoma (POAG) is mild, less predictable, related to baseline levels, and may return to presurgical values after an initial period of reduction. Therefore, the IOP-lowering effect of primary cataract extraction in POAG may be insufficient to achieve adequate IOP control. The IOP reduction after lens extraction is consistently greater in eyes with primary angle closure glaucoma (PACG) than in eyes with POAG. Primary lens extraction in acute PACG eliminates, or at least, reduces the risk of recurrence of acute attacks and deepens the anterior chamber and widens the angle which reduces the risk of progression of peripheral anterior synechiae and development of chronic PACG. Primary lens extraction may be more preferable to glaucoma incisional surgery in mild to moderate PACG eyes with appositional angle closure. The decision to do lens extraction as a primary treatment for glaucoma should be individualized based upon several factors other than the effect on IOP. These factors include patients’ characteristics, surgeons’ skills and preferences, status of glaucoma control, type of cataract and intraocular lens implanted, and potential harm of laser treatment for late capsular opacification and fibrosis.     

合并原发性青光眼的白内障手术选择

目的 探讨合并原发性青光眼的白内障手术方案。方法 对４６例５２眼采用ＥＣＣＥ＋ＩＯＬ、ＥＣＣＥ＋ＩＯＬ＋小梁切除的病例进行手样前后眼压、Ｃ值、前房角镜、视力等检查并进行比较。结果 随访１年。１８眼急闭中３眼以及２４眼慢闭中２２眼ＥＣＣＥ＋ＩＯＬ术后眼压及Ｃ值均恢复正常,房角变宽,两组无显著性差异。结论 术前眼压、Ｃ值、房角检查为正确选择手术方式提供较为客观准确的参考标准。     

Adverse effects and complications of argon laser trabecular retraction: practical results

Argon laser trabeculoplasty is learned and used much more easily than filtration surgery. This explains the danger of its being abusively employed, as well as the existence of complications such as an aggravated glaucoma condition (1 to 3% of the cases). In 253 eyes afflicted with various forms of chronic open angle glaucoma with follow-ups ranging from at least 6 months to 4 years, the following complications were disclosed: 3% of the cases required treatment for severe anterior uveitis; anterior synechiae occurred in 23%, including one case of circular anterior synechiae and 4 other cases in which acute angle closure glaucoma developed several months later; trabecular hemorrhage in 6%; post operative intra ocular pressure elevation in 13%. This last complication is the most dangerous especially in advanced glaucoma: it very frequently happens during the first post operative hours in the absence of preventive treatment and it can arise up to three weeks after the procedure. In 33 cases upon 253 (13%), the pressure increase, despite a systematic preventive treatment, ranged from +3 mmHg to +16 mmHg above the baseline level in more than two thirds of these particular cases (+5 mmHg in only 7.5% of the cases and +9 in only 3.5%). In 59 eyes treated by less intensive trabeculoplasty (50 burns upon 180 degrees trabeculoplasty ring), the pressure increased in only 3.4% of the cases but the long term efficacy was reduced. Argon laser trabeculoplasty complications are less numerous than those of surgery, but some of them, i.e. intra ocular pressure elevation, can be very serious and must lead to a study of the risk-benefit ratio corresponding to the glaucoma stage which is to be treated.     

Case-based approach to managing angle closure glaucoma with anterior segment imaging

This is a case-based approach to the diagnosis and management of angle closure glaucoma of a variety of causative factors, with a special emphasis on the use of advanced anterior segment imaging including ultrasound biomicroscopy and anterior segment optical coherence tomography. Although all angle closure is caused by iridotrabecular contact, the cause of angle closure glaucoma is classified based on the site of primary blockage of aqueous movement from anterior to posterior: pupillary block, plateau iris, lens-related, and posterior causative factors. Although gonioscopy is traditionally used to visualize the angle structures and estimate the angle width, objective and reproducible measurement of the anterior chamber angle can best be obtained with advanced anterior segment imaging. In this review article, we demonstrate the utility of anterior advanced imaging to identify underlying mechanisms in cases of angle closure glaucoma in guiding directed management.     

Imagings of glaucoma: characteristics of ocular configurations and automated diagnosis

Glaucoma is characterized by the coexistence of structural changes in the fundus and the corresponding functional abnormalities. The advances in imaging devices that reveal structural changes in glaucoma should facilitate reliable diagnosis of early or preperimetric glaucoma and a proper evaluation of glaucoma progression. Moreover, the increase in our knowledge of structural changes in glaucoma will provide a better platform for investigating up to now unknown glaucoma etiologies. In this review, we summarize a series of our clinical investigations of glaucoma imaging technologies. The diagnostic performance of Heidelberg Retina Tomograph (HRT) II and the characteristics of the HRT II parameters in high myopia were studied with population-based data to provide data for nerve head configuration; the correlation of parameters determined by planimetry of optic disc stereophotography with the results of the HRT II was evaluated; optic disc parameters were determined based on spectral-domain optical coherence tomography (SD-OCT); and optic disc configurations were evaluated in eyes with peripapillary atrophy and eyes with superior segmental optic nerve hypoplasia. Peripapillary retinal nerve fiber layer (RNFL) thickness was determined with SD-OCT in normal Japanese eyes; and the diagnostic performance of RNFL thickness was studied. The characteristics of each layer, including retinal nerve fiber layer, ganglion cell layer, and each complex layer in the macular area, and their correlation with the stages of glaucoma were evaluated. Finally, imaging of the anterior chamber angle using ultrasound biomicroscopy (UBM) were studied about the distribution of the UBM parameters in a Japanese population and the factors relating to the presence of peripheral anterior synechia in narrow angle eyes.     

眼前段分析系统（Pentacam）临床应用的意义

目的 探讨Pentacam综合眼前段三维分析系统在闭角型青光眼的早期筛查和青光眼白内障联合手术疗效量化评价方面的意义.方法 60岁以上志愿者25人（25眼）,为正常对照组,原发性急性闭角型青光眼25例（25眼）和原发性慢性闭角型青光眼25例（25眼）,应用Pentacam综合眼前段三维分析系统测量前房形态参数（前房深度、前房容积、前房角）,并分别与青光眼白内障联合手术前与术后1d、7d、30 d测量的前房形态参数：前房深度、前房容积、前房角进行比较.结果 正常对照组前房形态参数的测量值均大于原发性急、慢性闭角型青光眼两个组,差异均有统计学意义;青光眼两组之间比较,差异无统计学意义.两个青光眼组在青光眼白内障联合手术后各时间点前房深度较术前均加深,前房容积较术前均变大,前房角较术前均增宽,差异均有统计学意义.结论 Pentacam综合眼前段三维分析系统可以用来量化评价青光眼白内障联合手术后的眼前段形态的变化,为预后的评估提供参考.