Effect of intraocular lens design on posterior capsule opacification: an in-vitro model

BACKGROUND: The development of posterior capsule opacification (PCO) is one of the commonest complications of modern cataract surgery. The various designs of intraocular lenses (IOL) seem to exert a barrier effect on the proliferation and migration of lens epithelial cells and the following development of PCO. METHODS: We set up a cell culture model (advanced 3D capsular bag model) and investigated six differently designed IOL made of different materials as to their effect on cell proliferation. Proliferation and migration of the cells were analysed and documented over a period of 28 days. A cell viability test using the LIVE/DEAD kit (Molecular Probes) was carried out at the end of the investigation. RESULTS: In all tests, lens epithelial cells adhered to and migrated onto the capsular bag. During the culture period, lens epithelial cells migrated only to the optical rim of two of the implanted IOL. On the other four, lens epithelial cells migrated further and covered the whole optical area of the IOL. CONCLUSIONS: Certain lens designs seem to have a reducing effect on the development of PCO. Our advanced in vitro capsular bag model is a suitable cell culture model for the investigation of the reducing effect of various IOL on the development of PCO.     

术后囊袋弯曲形成在屈光性白内障手术中的意义

屈光性白内障手术时代,术后后囊膜混浊（PCO）以及人工晶状体（IOL）位置异常已成为影响患者视觉质量的重要因素。笔者将从囊袋弯曲角度阐述白内障术后后发性白内障和IOL在囊袋内的稳定性。囊袋弯曲是术后囊袋和IOL锐利边缘贴合形成的屏障结构。完全黏附型囊袋弯曲不仅可以有效减少晶状体上皮细胞的迁移,而且提高IOL稳定性（包括轴向位移、偏心、倾斜及旋转等）。现立足于囊袋弯曲的形成演变过程以及不同分型,阐述了其预防PCO和维持IOL稳定性的机制,为提高白内障患者术后视觉质量提供思路及可行措施。     

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。     

Comparison of design of intraocular lens versus the material for PCO prevention

AIM: To evaluate the influence of different intraocular lens(IOL) designs made of PMMA on posterior capsular opacification(PCO) and compare with foldable designs. METHODS: Phacoemulsification and IOL implantation was done in one eye of 24 New Zealand White rabbits, with IOL of two different designs (Square edged or round edge) and two different materials(PMMA or HEMA). After three months, the animals were sacrificed and enucleated. Evaluation of PCO included posterior view, migration of anterior capsular epithelial cells to the posterior capsule following epithelial-mesenchymal transition were assessed by staining the histological sections of posterior capsule by hematoxylin-eosin(HE) and Periodic acid- Schiff (PAS). The IOLs were extracted and stained with HE to evaluate the presence of adherent cells on the lens surface. RESULTS: PCO was highest with round edged rigid lens. There was no significant difference in the PCO between the square edged PMMA and square edged foldable lens. CONCLUSION: It is the design of the IOL not the material that offers protection on PCO formation.     

Linear posterior capsule opacification with the AcrySof intraocular lens.

Intraoperative capsule striae are commonly seen after implantation of the AcrySof model MA60BM posterior chamber intraocular lens (IOL). Although the striae generally have no visual significance and tend to disappear with remodeling of the capsule-haptic interface, we report a series of patients who developed linear posterior capsule opacification (PCO) along persistent striae. The striae appear to create a channel that allows endothelial cells to bypass the barrier created by the squared-edge design of the IOL and migrate posteriorly in a linear pattern. The observation of linear PCO along channels created by capsule striae provide strong support for the theory that a sharp-edge design creates a barrier to posterior epithelial cell migration.     

Fellow-eye comparison of posterior capsule opacification rates after implantation of 1CU accommodating and AcrySof MA30 monofocal intraocular lenses

PURPOSE: To measure posterior capsule opacification (PCO) and neodymium:YAG (Nd:YAG) capsulotomy rates between the AcrySof MA30 intraocular lens (IOL) (Alcon) and the 1CU IOL (HumanOptics) in a fellow-eye comparison. SETTING: Ophthalmology Department, St. Thomas' Hospital, London, United Kingdom. METHODS: Thirty patients who had bilateral cataract surgery with a 1CU IOL prospectively randomly allocated to 1 eye and an AcrySof MA30 monofocal IOL to the other eye were examined. Best corrected distance visual acuity was recorded using the Early Treatment Diabetic Retinopathy Study logMAR chart. Digital retroillumination images of the posterior capsule were taken with the pupil dilated and analyzed with POCO software. RESULTS: Eyes with the 1CU IOL had significantly higher PCO rates than eyes with the MA30 IOL at all time points. By 2 years after surgery, 50% of eyes with a 1CU IOL had required Nd:YAG capsulotomy compared with no eyes with an MA30 IOL. There was no significant difference in visual acuity at any time point when post Nd:YAG capsulotomy was taken in to account. CONCLUSIONS: The 1CU IOL has 4 broad optic-haptic junctions where the square-edged barrier is breached; this appeared to allow passage of lens epithelial cells, leading to an increase in PCO. However, the increased PCO cannot be attributed to this alone as the 1CU is hydrophilic, a factor known to be associated with higher PCO rates.     

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.     

Comparison of posterior capsule opacification rates between hydrophilic and hydrophobic single-piece acrylic intraocular lenses

PURPOSE: To determine the effect of intraocular lens (IOL) material on the development of posterior capsule opacification (PCO) at 1 year. SETTING: Department of Ophthalmology, St. Thomas' Hospital, London, United Kingdom. METHODS: One hundred six eyes of 53 patients with bilateral cataract and no other ocular comorbidity were prospectively randomized to receive a hydrophobic acrylic or hydrophilic acrylic single-piece IOL in the first eye to have surgery. The alternate IOL was implanted in the fellow eye 4 to 6 weeks later. All surgery was performed by a single surgeon. Postoperative follow-up was 1 day, 1 and 6 months, and 1 year. At each visit, the best corrected high- and low-contrast visual acuities were assessed and a high-intensity digital retroillumination photograph was taken. Posterior capsule opacification was assessed from the digital images by a single operator using a dedicated software program and calculated as the percentage area of opacified capsule. RESULTS: One year postoperatively, the median percentage area of PCO was 50.3% in the hydrophilic IOL group and 4.9% in the hydrophobic IOL group (P<.001). The difference in PCO was not accounted for by loss of contact between the capsulorhexis and IOL surface. Further analysis showed that lens epithelial cells tended to invade the posterior capsule at the haptic-optic junction. This was more marked in the hydrophilic IOL group. CONCLUSIONS: The rate of PCO was significantly higher with the hydrophilic IOL. However, the results cannot be attributed to the IOL material alone as they show the importance of both IOL material and design.     

直角边缘人工晶状体预防兔后囊膜混浊的实验研究

目的探讨直角边缘人工晶状体（intraocular lens，IOL）预防后囊膜混浊（posterior capsule opacification，PCO）的作用。方法30只新西兰兔进行超声乳化晶状体摘出联合囊袋内IOL植入术后，随机植入Crane OV-55CP、Crane OV-55C、Alcon TYPE 5C 3种IOL之一。观察术后并发症和PCO情况。术后3月行光镜和透射电镜检查，观察晶状体后囊膜的形态学变化。结果术后3月Crane OV-55CP组的PCO程度比Crane OV-55C和Alcon TYPE 5C组轻（P〈0．05），各组Soemmefing环形成程度无差异（P〉0．05）。病理学检查发现Crane OV-55CP组兔赤道部增生的晶状体上皮细胞在人工晶状体的直角边缘处受到了阻挡。Crane OV-55C和Alcon TYPE 5C组大量晶状体上皮细胞迁移至后囊膜。结论直角边缘IOL延缓了兔PCO的发生、发展，是预防PCO简便安全有效的方法。     

Preventing lens epithelial cell migration using intraocular lenses with sharp rectangular edges

PURPOSE: To compare the preventive effect on posterior capsule opacification (PCO) of an acrylic intraocular lens (IOL) and a silicone IOL, both with sharp rectangular optic edges. SETTING: Jinshikai Medical Foundation, Nishi Eye Hospital, Osaka, Japan. METHODS: After phacoemulsification, an acrylic IOL (AcrySof(R)) was implanted in 1 eye and a silicone IOL (CeeOn 911) in the contralateral eye of 7 rabbits, one of which was omitted from evaluation. RESULTS: The Miyake-Apple view and histopathological findings 3 weeks after surgery revealed that the lens capsule wrapped tightly around the optic edges, conforming to a distinctly sharp bend, with both IOL types in 5 rabbits. Migrating lens epithelial cells (LECs) were inhibited at the site. The AcrySof IOL had a better capsular bend effect in the histological sections, but there was no apparent difference in PCO development between the 2 IOLs. CONCLUSIONS: The CeeOn 911 silicone IOL, with sharp rectangular optic edges, showed an effect on preventing PCO that was similar to that of the AcrySof IOL. When a discontinuous capsular bend is created by an IOL with sharp optic edges, the bend may induce contact inhibition of migrating LECs regardless of the lens' material composition.     

Posterior capsule opacification

Posterior Capsule Opacification (PCO) is the most common complication of cataract surgery. At present the only means of treating cataract is by surgical intervention, and this initially restores high visual quality. Unfortunately, PCO develops in a significant proportion of patients to such an extent that a secondary loss of vision occurs. A modern cataract operation generates a capsular bag, which comprises a proportion of the anterior 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. 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. However, on the remaining anterior capsule, lens epithelial cells stubbornly reside despite enduring the rigours of surgical trauma. This resilient group of cells then begin to re-colonise the denuded regions of the anterior capsule, encroach onto the intraocular lens surface, occupy regions of the outer anterior capsule and most importantly of all begin to colonise the previously cell-free posterior capsule. Cells continue to divide, begin to cover the posterior capsule and can ultimately encroach on the visual axis resulting in changes to the matrix and cell organization that can give rise to light scatter. This review will describe the biological mechanisms driving PCO progression and discuss the influence of IOL design, surgical techniques and putative drug therapies in regulating the rate and severity of PCO.     

后囊膜混浊相关分子调控通路研究进展

白内障手术是目前世界上最常见、最成熟的眼科手术之一。手术包括摘除混浊的晶状体及人工晶状体的植入,可以较好地恢复患者视力。后囊膜混浊（posterior capsular opacification,PCO）,又称继发性白内障,是白内障手术后常见的并发症之一,严重影响了手术的治疗效果。在白内障手术后2~5 a,由PCO导致的视力下降患者占20%~40%。PCO是一种纤维变性疾病。研究PCO的发生机制已经成为一项重要的医学课题。目前证实手术后晶状体赤道部及前囊下残余的晶状体上皮细胞通过增殖、迁移、上皮间质转化成为成纤维细胞和肌成纤维细胞,伴随细胞外基质的合成最终导致了PCO的发生。一系列生长因子及信号通路参与到PCO的形成和发展过程并发挥了关键作用。本文对与PCO发生相关的分子调控通路的最新知识进行了总结,并探讨了干扰PCO发生的可能途径。     

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.     

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.     

后发性白内障的防治新进展

后囊膜混浊(posterior capsule opacification,PCO)又称后发性白内障是现代白内障囊外摘出或超声乳化吸除联合人工晶状体植入术后最常见的晚期并发症,如何防治后发性白内障一直是眼科学者关注的焦点,并不断在此领域取得新的进展。拟对近年来后发性白内障防治中手术方式的改进、人工晶状体自身特性的影响、囊袋张力环的应用、密封囊灌洗技术的开展和基因治疗等方面的研究进展和发展趋势加以综述。     

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。     

直角边缘囊袋张力环预防兔后囊膜混浊的实验研究

目的:探讨直角边缘囊袋张力环(capsule tension ring,CTR)预防兔后囊膜混浊(posterior capsule opacification,PCO)的作用。方法:新西兰兔20只随机分为两组,进行超声乳化晶状体摘除术后,实验组植入CTR和CraneOV-55C人工晶状体(intraocular lens,IOL),对照组只植入CraneOV-55CIOL。观察术后并发症和PCO情况。术后3mo行光镜和透射电镜检查,观察晶状体后囊膜的形态学变化。结果:术后3mo实验组和对照组都发生了明显的PCO(P>0.05),各组Soemmering环形成程度无统计学差异(P>0.05)。病理学检查发现,两组兔赤道部晶状体上皮细胞增生形成了巨大的Soemmering环,大量晶状体上皮细胞移行至后囊膜。结论:直角边缘CTR未能预防兔PCO的发生,有必要对其进一步改进。     

Predicting posterior capsule opacification: value of early retroillumination imaging

PURPOSE: To investigate the value of early retroillumination imaging of the posterior capsule in predicting the eventual development of posterior capsule opacification (PCO). SETTING: Ophthalmology Department, St. Thomas' Hospital, and Department of Physics, King's College, London, United Kingdom. METHODS: All patients with retroillumination images of the posterior capsule taken 6 months and 2 years after uneventful phacoemulsification with in-the-bag intraocular lens (IOL) implantation were selected. The images were taken using the same hardware and analyzed with the same software to calculate the percentage area of the posterior capsule covered by lens epithelial cells. The percentage area of PCO with all IOL types 6 months postoperatively was correlated with that at 2 years. RESULTS: One hundred forty patients had analyzable images at 6 months and 2 years. Of these, 63 had a poly(methyl methacrylate) (PMMA) IOL (Pharmacia 812A or Storz P497UV), 33 an acrylic (Alcon AcrySof MA30 or SA30), 22 a silicone (Allergan SI-30), and 22 a hydrophilic acrylic (Bausch & Lomb Hydroview H60). The correlation of the percentage area of PCO at 6 months with that at 2 years resulted in an r value of 0.71 (P <.0001) in the entire group. The r value was 0.48 in the PMMA group and 0.86 in the foldable IOL group (P <.0001) (r value: AcrySof, 0.66; silicone, 0.82; Hydroview, 0.75). CONCLUSIONS: Retroillumination imaging of the posterior capsule 6 months after cataract surgery predicted the PCO outcome at 2 years in eyes with foldable IOLs.     

多聚赖氨酸与EDTA的交联物防治兔眼后囊膜混浊的研究

目的 观察在白内障术中应用多聚赖氨酸与EDTA的交联物对晶状体后囊膜混浊(PCO)的影响.方法 利用EDC将EDTA与多聚赖氨酸结合,制成交联物PLE.日本大耳白兔9只(18眼),随机分为3组.实验组在白内障囊外摘出术中分别于囊袋内注入药物:EDTA组注入EDTA 20 mmol/L;PLE组注入PLE其中含EDTA 10 mmol/L、NH2-10 mmol/L;对照组囊袋内不注入药物.术后用裂隙灯观察眼内组织的变化.28 d后处死兔子,摘除眼球,制作病理切片,光镜下观察晶状体上皮细胞(LECs)增生情况.结果 PLE组仅有少量细胞残留,未见细胞增生,其他组均可见不同程度的细胞残留及增生.结论 与EDTA相比,PLE可更有效地清除LECs.     

Analysis of cytoskeletal proteins in posterior capsule opacification after implantation of acrylic and hydrogel intraocular lenses

PURPOSE: To analyze selected lens cytoskeletal proteins in posterior capsule opacification (PCO) 2 weeks after intraocular lens (IOL) implantation in rabbits. SETTING: Department of Ophthalmology, Dokkyo University School of Medicine, Tochigi, Japan. METHOD: Eight 10-week-old albino rabbits were prepared and anesthetized for phacoemulsification and aspiration of the crystalline lens and implantation of an acrylic or a hydrogel IOL. Two weeks postoperatively, the rabbits were killed and the IOLs removed for immunohistochemistry. Deparaffinized tissue sections were processed with antibodies against alpha-smooth muscle actin (alpha-SMA) and beta-crystallin to observe the types of PCO with the 2 IOL types. The proteins in the PCO tissue and the normal lens were homogenized, centrifuged, and analyzed using SDS-polyacrylamide gel electrophoresis (SDS-PAGE) densitometric analysis and Western immunoblotting for actin and vimentin. RESULTS: Immunohistochemistry demonstrated a fibroblastic cell type expressing alpha-SMA and partial regeneration of epithelial cells, resulting in a lenticular structure that stained irregularly for beta-crystallin. The immunoreactivity of fibroblast-like cells to beta-crystallin appeared weaker than that of the regenerated lenticular structure. SDS-PAGE showed variability in the content of cytoskeletal proteins in the insoluble fractions of the PCO. Degradation of the cytoskeletal components was greater with the acrylic IOL than with the hydrogel IOL. CONCLUSION: Cytoskeletal proteins expressed during the formation of PCO and IOL implantation may have potential as therapeutic target proteins to improve the biocompatibility of IOLs.