后发性白内障的发病机制和药物防治的研究现状及前景

后发性白内障是现代白内障术后最常见的并发症。术后晶状体囊残留的晶状体上皮细胞的增殖、迁移、纤维化生是形成后发性白内障的主要原因。目前防治后发障的研究主要集中在药物除去或破坏残留晶状体上皮细胞。实验研究许多细胞毒药以及抑制晶状体上皮细胞生长和纤维化药物可以预防后发障,但目前临床上还没安全、有效的防治白内障方法。     

Cerulean posterior capsule opacity

We present a case of light-blue posterior capsule opacification (PCO) in a patient who had cerulean cataracts removed 1 year earlier. The color of the PCO was similar to that of the cerulean cataracts prior to extraction. Posterior capsule opacification is a common complication after cataract surgery; however, we could not find a similar case of cerulean posterior capsule opacity in the literature. The findings in this case suggest that the mechanism of the light-blue color formation in the cataract was also present in the lens epithelial cells forming the posterior capsule opacity.     

靶向治疗后囊混浊的研究进展

后囊混浊是白内障手术的常见并发症。残留晶状体上皮细胞在后囊的增殖、移行、纤维化生是后囊混浊形成的重要因素。用于防治后囊混浊的许多约物如道诺霉素、丝裂霉素等，因眼内的毒副作用而受到限制。靶向治疗的特异性、针对性为解决这一问题带来了希塑。综述了靶向治疗后囊混浊的研究现状及对未来的研究展望。     

Posterior capsule opacification

Posterior capsule opacification (PCO) is the most common complication following primary cataract surgery. Advances in intraocular lens (IOL) designs that have reduced the amount of PCO following surgery have been made. The understanding of how the IOL design effects PCO has also advanced. Lenses that provide a mechanical barrier between it and the posterior lens capsule seem to inhibit PCO to a greater degree. Intracapsular rings are now being explored to test and enhance this barrier effect. Major advances in the elimination of lens epithelial cells at the time of surgery especially by pharmacologic means have also been made. An immunotoxin specific for human lens epithelial cells shows promise and is under latter phase clinical development.     

结缔组织生长因子与后发性白内障的研究进展

后发性白内障(又称后囊膜混浊)已成为白内障术后视力再度下降,影响术后远期视力恢复的突出问题,主要是由于残留的晶状体上皮细胞向后囊膜移行、增殖形成。结缔组织生长因子(connective tissue growth factor,CTGF)是近年来倍受关注的促纤维化细胞因子。本文对近年来CTGF与后发性白内障关系的研究进展综述如下。     

Posterior capsule management in congenital cataract surgery

Management of the posterior capsule significantly affects the outcome of pediatric cataract surgery. Posterior capsule opacification (PCO) is rapid and virtually inevitable in very young children when adult-style cataract surgery is performed and the posterior capsule is left intact. In eyes with pediatric cataract, primary posterior capsulotomy and vitrectomy are considered routine surgical steps, especially in younger children. The site of intraocular lens (IOL) fixation and the surgical technique used also affect the prevalence of PCO. The present systematic review evaluates the options available to prevent PCO or ensure a clear central visual axis after pediatric cataract surgery. Newer approaches to posterior capsule management such as pars plicata posterior capsulorhexis, sutureless vitrectomy, sealed-capsule irrigation, and bag-in-the-lens IOL are discussed. Management of the posterior capsule in the presence of a preexisting posterior capsule defect and posterior capsule plaque and options to treat PCO are also reviewed. FINANCIAL DISCLOSURE: No author has a financial or proprietary interest in any material or method mentioned.     

晶状体囊抛光及透明质酸酶预防囊的浑浊

目的探讨晶状体囊抛光并囊袋内注射透明质酸酶预防囊的浑浊和后发性白内障的作用及安全性.方法年龄相关性白内障70例80眼,按常规进行超声乳化吸出人工晶状体植入术.治疗组40眼水分离时用含透明质酸酶1000 IU的必施（BSS）进行,乳化吸出晶状体核和皮质后在黏弹剂的保护下,囊袋内注入含透明质酸酶500IU的BSS,2分钟后用抛光针尖进行晶状体囊抛光,然后注吸清除上皮细胞碎屑,囊袋内植入人工晶状体.对照组40眼则用同等量BSS进行水分离,仅行后囊抛光.术后18月随访,进行角膜内皮、眼底及视网膜电图等检查,并对前、后囊浑浊的情况进行分级.结果术后18月治疗组前、后囊膜浑浊的发生率与对照组相比,差异有统计学意义.角膜内皮损失率与对照组相比,差异无统计学意义.两组眼底检查和视网膜电图检查显示视网膜功能正常.结论晶状体囊袋内注射透明质酸酶联合晶状体囊抛光可以预防囊的浑浊和后发性白内障发生,且眼内应用安全.     

大鼠后囊膜混浊模型的建立

目的建立一种新的、具有实用价值的大鼠后囊膜混浊(posterior capsule opacification,PCO)动物模型。方法12只SD(Sprague Dawley)大鼠随机分为4组,每组3只,每只大鼠双眼施行晶状体囊外摘除术(extracapsular lens extrac-tion,ECLE);在手术后即刻、第1天、第7天、第14天摘除眼球,进行组织病理学观察,研究残留晶状体上皮细胞(lensep-ithelial cells,LECs)增殖、移行和后囊膜的动态变化;应用方差分析比较LECs增殖数量。结果所有大鼠均成功施行ECLE手术。手术后即刻可见前囊膜下及赤道部有单层的LECs排列;术后第1天赤道部形成由2～3层细胞组成的细胞团块,LECs沿着囊膜向后囊迁移;术后第7天囊袋赤道部及后囊膜下形成多层细胞结构,赤道部晶状体纤维样物质增加,部分后囊膜出现明显皱褶;术后第14天囊袋赤道部及后囊膜下LECs形成团块,赤道部形成晶状体纤维样结构,赤道部Soemmering环形成。随时间推移,单位面积LECs数量明显增加(P<0.05)。结论大鼠ECLE手术后可成功建立后囊膜混浊模型。     

Capsulotomy diameter mark

Recent improvements in intraocular lens (IOL) design and material delay posterior capsule opacification (PCO) after cataract surgery. However, studies have shown that without anterior capsule coverage of the IOL, PCO rates tend to increase. Surgeons have traditionally sized anterior capsulotomies without using a reference. The capsulotomy diameter mark is a convenient and inexpensive method to more consistently perform an anterior capsulorhexis that will allow anterior capsule overlap of the IOL optic.     

Posterior capsule opacification and anterior capsule opacification

Posterior capsule opacification (PCO) is still the most frequent complication of cataract surgery. A variety of studies has led to a better understanding of the pathogenesis of PCO, and strategies of molecular biology have produced new therapeutic options, such as immunological techniques or gene therapeutic approaches. Surgical strategies and intra-ocular lens-dependent factors also are capable to reduce the rate of PCO. In-the-bag implantation of intra-ocular lenses with a sharp optic edge seems to be effective in inhibiting equatorial lens epithelial cell migration to the center of the posterior capsule. Several PCO documentation systems have been developed that will lead to more exact and better comparable recording of PCO rates. In the year 2000, PCO or secondary cataract is still the most frequent complication after extracapsular cataract surgery. In a 1998 meta-analysis, PCO rates of 11.8% 1 year after extracapsular cataract surgery with intraocular lens implantation, 20.7% after 3 years, and 28.4 % after 5 years have been reported. For the United States, it has been estimated that the overall expenses for treatment of PCO are only exceeded by the costs for cataract treatment itself. In the past decade, a lot of experimental and clinical studies have been performed on this topic. They have led to 1) to a better understanding of the pathogenesis of the development of anterior and posterior capsule opacification; 2) more objective and better comparable systems of documentation and analysis of PCO; and a number of 3) surgical and 4) pharmaceutical strategies to prevent PCO.     

改良大鼠后囊膜混浊模型的建立及晶状体上皮细胞的变化

目的:改良法建立大鼠后发性白内障动物模型并观察LEC在PCO过程中的动态变化。方法:SD大鼠50只在连续环形撕囊、水分离后行晶状体囊外摘除术(ECLE),娩核后使用无菌空气恢复前房。分别于术后0,3,7,14及28d对术眼进行裂隙灯检查并处死动物,摘除眼球行光镜观察,免疫组化检测LEC的α-SMA表达。结果:100%术眼后囊膜存在,84%的鼠眼可用于检测。术后0h于前囊下和赤道部的内表面观察到LEC。PCO在术后3d出现,出现囊膜皱缩,整个晶体囊膜出现纺锤形细胞。术后7d时后囊膜明显混浊,见较多纺锤形细胞分布。所有动物于术后14d出现明显后囊膜皱缩,可见新生晶体纤维。术后28d见明显后囊膜增厚,新生晶体纤维填充囊袋,后囊膜未见细胞。LEC形态及分布恢复到术后0h状态。免疫组化检测见术后3d时α-SMA阳性表达。结论:改良法成功建立大鼠PCO模型,LEC在PCO形成中出现形态和分布上的动态变化。其将为在分子水平上探索PCO的发病机制及防治方法提供合适研究载体。     

When may the posterior capsule be preserved in pediatric intraocular lens surgery?

PURPOSE: To refine indications for primary posterior capsulotomy (PPC) in conjunction with posterior chamber intraocular lens (PCIOL) implantation for cataract in childhood. DESIGN: Noncomparative case series. PARTICIPANTS: Patients 1 to 13 years old who underwent cataract extraction with intent to preserve the posterior lens capsule and PCIOL implantation between January 1992 and December 1998 at a pediatric hospital. METHODS: Medical records were reviewed to determine the frequency and timing of posterior capsule opacification (PCO) after PCIOL surgery with preservation of an intact posterior capsule. Comparison of pseudophakic PCO rates for groups defined by age and several possible risk factors. Assessment of safety and efficacy for PPC with anterior vitrectomy performed through a limbal incision in cases where the posterior capsule could not be preserved. MAIN OUTCOME MEASURES: Need for neodymium:yttrium-aluminum-garnet laser capsulotomy or surgical membranectomy to treat PCO. RESULTS: PCO occurred in 40% of 30 eyes with intact posterior capsule. Mean follow-up duration was 22 months for eyes that had PCO develop and 24 months for those in which the posterior capsule remained clear. Laser capsulotomy was required for 64% of 14 eyes in the 1- to 6-year-old age range but for only 19% of 16 in the 6- to 13-year-old range (P < 0.05). Mean time from surgery to PCO was 7 months for the younger group and 13 months for the older group. A need for repeated capsulotomy (one eye) or membranectomy with anterior vitrectomy (two eyes) was found only in the younger age group. There was no association of PCO with trauma history, cataract type, residual lens cortex, IOL position, or postoperative fibrin clot. Final vision was possibly compromised as a result of PCO in one eye with amblyopia. None of 24 eyes in which PPC with anterior vitrectomy was performed out of intraoperative necessity before primary PCIOL implantation had secondary opacification develop. No reduction in postoperative vision was attributable to PPC. CONCLUSIONS: PPC seems to be advisable for children less than 6 years old when cataract extraction with PCIOL implantation is performed. Preservation of the posterior capsule remains appropriate for older children with pseudophakia.     

A new model of posterior capsule opacification in rodents

PURPOSE: To describe a new model of posterior capsule opacification (PCO) in rodents METHODS: An extracapsular lens extraction (ECLE), by continuous curvilinear capsulorrhexis and hydrodissection, was performed in 42 consecutive Brown Norway rats. Animals were killed at 0, 6, and 24 hours and 3, 7, and 14 days after surgery. Eyes were enucleated and processed for light microscopy and immunohistochemistry. RESULTS: In 34 (81%) of the animals the operated eye appeared well healed before death, with a clear cornea and a well-formed anterior chamber. In eight (19%) there was no view of anterior segment structures because of hyphema, fibrin, or corneal opacification. PCO was clinically evident 3 days after ECLE and was present in all animals at 2 weeks. Immediately after ECLE, lens epithelial cells (LECs) were present in the inner surface of the anterior capsule and lens bow. Twenty-four hours after surgery, LECs started to migrate toward the center of the posterior capsule. At 3 days, multilayered LECs, some spindle shaped, were present throughout the lens capsule. Capsular wrinkling was apparent. Lens fibers and Soemmering's ring were observed in all animals 14 days after surgery, indicating some degree of cellular differentiation. Activated macrophages were present in greater numbers at 3 and 14 days after surgery (P < 0.05), when proliferation and migration of LECs appeared to be greatest, and lens fiber differentiation was evident, respectively. CONCLUSIONS: In rodents PCO occurs after ECLE and is associated with low-grade inflammation, mostly of mononuclear macrophages. Although no intraocular lens implantation was performed, this model appears to be valuable for studying the sequence of events that leads to PCO after cataract surgery and the extracellular matrix cues that promote lens fiber differentiation.     

Activation of SRC kinases signals induction of posterior capsule opacification

PURPOSE: Posterior capsule opacification (PCO) is a complication of cataract surgery resulting from the proliferation, migration, and epithelial-to-mesenchymal transition (EMT) of lens epithelial cells that remain associated with the lens capsule. These changes cause a loss of vision. The authors developed a chick embryo lens capsular bag model to study mechanisms involved in the onset of PCO. Because Src family kinases (SFKs) signal cell proliferation, migration, and EMT, the authors examined whether the inhibition of SFKs can prevent PCO. METHODS: After mock cataract surgery, chick lens capsular bags were pinned to a culture dish and grown in the presence or absence of the SFK inhibitor PP1. Cell movement was followed by photomicroscopy. Progression of proliferation and EMT in the PCO cultures was determined by Western blot analysis and immunofluorescence staining. RESULTS: As occurs in PCO, lens cells in this model proliferated, migrated across the posterior capsule, and expressed EMT markers, alpha-smooth muscle actin (alpha-SMA), and fibronectin (FN). Lens cells treated with PP1 maintained an epithelial phenotype, accumulated cadherin junctions, and did not migrate to the posterior capsule, increase proliferation, or express EMT markers. Therefore, exposure to PP1 prevented PCO. Short-term inhibition of SFKs was sufficient to prevent EMT, but longer inhibition was necessary to prevent lens cell migration. CONCLUSIONS: Progression of PCO involved early activation of SFKs. Lens cell migration preceded EMT, and each of these two events required activation of an SFK signaling pathway. Suppression of SFK activation blocked PCO, suggesting SFKs as a therapeutic target for the prevention of PCO.     

白内障术后晶状体后囊膜混浊及远期视力下降影响因素分析

目的探讨白内障术后晶状体后囊膜混浊(posterior capsular opacification,PCO)发生及术后远期视力下降的影响因素。方法收集行白内障超声乳化摘出联合人工晶状体植入术的年龄相关性白内障患者37例(47眼),记录患者术前、术后的眼部检查情况及是否行后囊膜抛光处理等术中情况,于术后2a对PCO进行分级评价。结果 47眼中,有25眼在术后2a发生了PCO,其中18眼混浊已累及中心3mm区,4眼已行YAG激光后囊膜切开术,后囊膜切开率8.5%。统计分析显示,PCO和混浊累及中心3mm区的发生率在是否行后囊膜抛光眼之间的差异均有统计学意义(均为P<0.05)。在各因素中,行后囊膜抛光是发生PCO以及混浊累及中心3mm区仅有的保护性因素。累及中心3mm区的PCO、眼底疾病和黄斑病变与术后2a视力变化之间的关联均有统计学意义(均为P<0.05)。结论白内障术后发生累及中心3mm区的PCO可导致术后远期视力下降;术中行后囊膜抛光处理可显著降低PCO的发生率和严重程度。     

Posterior capsule opacification: What's in the bag?

Cataract, a clouding of the lens, is the most common cause of blindness in the world. It has a marked impact on the wellbeing and productivity of individuals and has a major economic impact on healthcare providers. The only means of treating cataract is by surgical intervention. A modern cataract operation generates a capsular bag, which comprises a proportion of the anterior capsule and the entire posterior capsule. The bag remains in situ, partitions the aqueous and vitreous humours, and in the majority of cases, houses an intraocular lens (IOL). The production of a capsular bag following surgery permits a free passage of light along the visual axis through the transparent intraocular lens and thin acellular posterior capsule. Lens epithelial cells, however, remain attached to the anterior capsule, and in response to surgical trauma initiate a wound-healing response that ultimately leads to light scatter and a reduction in visual quality known as posterior capsule opacification (PCO). There are two commonly-described forms of PCO: fibrotic and regenerative. Fibrotic PCO follows classically defined fibrotic processes, namely hyperproliferation, matrix contraction, matrix deposition and epithelial cell trans-differentiation to a myofibroblast phenotype. Regenerative PCO is defined by lens fibre cell differentiation events that give rise to Soemmerring's ring and Elschnig's pearls and becomes evident at a later stage than the fibrotic form. Both fibrotic and regenerative forms of PCO contribute to a reduction in visual quality in patients. This review will highlight the wealth of tools available for PCO research, provide insight into our current knowledge of PCO and discuss putative management of PCO from IOL design to pharmacological interventions.     

Use of a polylysine-saporin conjugate to prevent posterior capsule opacification.

PURPOSE: To determine the feasibility of applying a polylysine-saporin (PLS) conjugate to the lens capsule at surgery to prevent lens epithelial cell (LEC) proliferation and posterior capsule opacification (PCO). SETTING: Department of Research & Development, Bausch & Lomb Surgical, and Department of Ophthalmology, Saint Louis University, St. Louis, Missouri, USA. METHODS: Fluorescein-labeled polylysine was applied to the lens capsule of rabbits after phacoemulsification and analyzed histologically to determine the extent of binding to the lens capsule and surrounding tissues. The cytotoxin saporin was conjugated to polylysine using bifunctional cross-linkers. This PLS conjugate was applied to LECs in culture and to the lens capsules of rabbits. These eyes were monitored for PCO. RESULTS: Polylysine primarily bound to the lens capsule membranes, with little or no binding to surrounding tissues. When PLS was added to LECs in culture, it was internalized and destroyed the cells. Of 9 rabbit eyes treated with PLS during surgery, 1 remained free of PCO for the life of the animal (40 weeks), while 6 showed a delay of cortical regrowth approximately 2 to 3 times that of control eyes. CONCLUSIONS: Polylysine bound selectively to the lens capsule membrane. The PLS conjugation resulted in a toxic agent that targeted the lens capsule and destroyed proliferating LECs. The application of a PLS conjugate during surgery may prevent PCO.     

Pathology of posterior capsule,a literature review

The posterior capsule opacification (PCO) is a frequent complication in the modern cataract surgery, uncomfortable for the patient and expensive for the health care system. According to prof. Apple, the main health care expenditure in U.S. is represented by cataract surgery, laser capsulotomy for PCO ranking next. Under these circumstances, it is not surprising that the lens bag pathology and the prevention of aftercataract hold the attention of many research groups all over the world. This paper is a literature review of the last 15 years, presenting the data we have considered to be the most significant.     

Role of posterior capsulotomy with vitrectomy and intraocular lens design and material in reducing posterior capsule opacification after pediatric cataract surgery

PURPOSE: To study the effect of primary posterior capsulotomy with anterior vitrectomy (PPC + AV) and intraocular lens (IOL) design and material on the development of posterior capsule opacification (PCO) after pediatric cataract surgery. SETTING: Tertiary care institution in India. PATIENTS: Sixty-four eyes of 52 children ranging in age from 3 months to 12 years who had cataract extraction with IOL implantation were prospectively evaluated for a minimum postoperative period of 2 years. METHODS: Thirty-two eyes received a hydrophobic acrylic lens with a truncated, square edge and 32, a single-piece poly(methyl methacrylate) (PMMA) lens that was not heparin surface modified. Sixteen eyes in each IOL group had PPC + AV; in the remaining 16 eyes in each group, the posterior capsule was left intact. RESULTS: Postoperatively, 25 eyes in the intact capsule group and 5 in the PPC + AV group developed PCO; the difference between groups was significant (P<.05). Of eyes with an intact capsule, 12 with an acrylic IOL and 13 with a PMMA IOL developed PCO (P>.05). In the PPC + AV group, 2 eyes with an acrylic IOL and 3 with a PMMA IOL developed PCO (P>.05). Overall, 14 eyes with an acrylic lens and 16 eyes with a PMMA lens developed PCO (P>.05). After surgery, there was a significant short-term delay in the development of PCO in the acrylic group (14 eyes; mean 6.66 months +/- 1.57 [SD]) compared to the PMMA group (16 eyes; mean 3.16 +/- 0.83 months) (P<.05). CONCLUSIONS: It is the management of the posterior capsule rather than IOL design and material that influences the incidence of PCO after cataract surgery in children. Development of PCO in the postoperative period was delayed with a hydrophobic acrylic IOL with square edges compared with a PMMA lens without square edges.     

大鼠后发性白内障发生过程中晶状体纤维分化的初步研究

目的在组织学和mRNA水平上初步了解大鼠后发性白内障模型形成过程中晶状体纤维的分化。方法对48只SD大鼠行晶状体囊外摘除术,在术后即刻、1d、3d、1周、2周、1个月、2个月、3个月行裂隙灯显微镜观察和HE染色;取不同时间点后发性白内障组织,采用半定量逆转录聚合酶链反应法（RT-PCR）检测晶状体蛋白基因-αA、αB、βB1、βB2、βA2、γD的表达水平。结果所有大鼠术后均发生晶状体后囊膜混浊（PCO）。术后即刻,晶状体前囊膜下残留晶状体上皮细胞（LEC）;术后1d,LEC已增殖迁移至晶状体后囊膜中央区;术后3d,晶状体后囊膜中央轻度混浊、皱缩,晶状体囊袋内布满增生的LEC,周边部发生晶状体纤维分化。术后7d,后囊膜中央混浊继续加重,呈放射状皱褶,周边形成Seommering环。术后14d,瞳孔区囊膜组织纤维机化,Seommering环更为明显;术后1个月。新生晶状体纤维填满晶状体囊袋,形成类似正常晶状体的赤道部。术后2、3个月,晶状体纤维继续增生,体积接近正常晶状体。半定量RT-PCR显示术后αA、αB、βB1、βB2、βA2、γD mRNA的表达逐渐增加。结论SD大鼠行晶状体囊外摘除术后短期内即会发生明显的后发性白内障,并表达α、β和γ晶状体蛋白。该动物模型可用于后发性白内障的发病机制和晶状体再生的应用基础研究。