Improving Outcomes in Cataract Surgery: Intraocular Lenses (IOLs) Resistant to Cell Growth

改善白内障手术的效果：抗细胞生长的人工晶状体 (IOL)

基本信息

批准号：
10573497
负责人：
Melissa Grunlan
金额：
$ 19.65万
依托单位：
TEXAS ENGINEERING EXPERIMENT STATION
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-03-01 至 2025-02-28
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10573497
关键词：
Adhesions Adsorption Adult Biological Blindness Cataract Cataract Extraction Cell Line Cells Chemistry Childhood Clinical Clinical Treatment Complex Complication Data Doctor of Medicine Education Elastomers Epithelial Cells Ethylene Oxide Excision Eye Formulation Growth Human Hydrophobic Surfaces In Vitro Incidence Income Intraocular Lens Implantation Intraocular lens implant device Lasers Length Lens development Mediating Medical Methods Minority Groups Modeling Molds Nature Operative Surgical Procedures Ophthalmologist Oryctolagus cuniculus Outcome Pathologist Patients Phacoemulsification Positioning Attribute Predisposition Production Property Proteins Qualifying Reactive Oxygen Species Reporting Research Residual state Resistance Resources Rest Retinal Detachment Silicones Siloxanes Structure Surface Surgical incisions Testing Underrepresented Populations Vision Visual impairment Woman Work amphiphilicity aqueous biomaterial compatibility capsule care costs cell growth design diphenyl elastomeric flexibility implantation improved improved outcome in vivo innovation lens manufacturing process medically underserved medically underserved population meetings men migration pressure prevent side effect skills standard care success

Adhesions Adsorption Adult Biological Blindness Cataract Cataract Extraction Cell Line Cells Chemistry Childhood Clinical Clinical Treatment Complex Complication Data Doctor of Medicine Education Elastomers Epithelial Cells Ethylene Oxide Excision Eye Formulation Growth Human Hydrophobic Surfaces In Vitro Incidence Income Intraocular Lens Implantation Intraocular lens implant device Lasers Length Lens development Mediating Medical Methods Minority Groups Modeling Molds Nature Operative Surgical Procedures Ophthalmologist Oryctolagus cuniculus Outcome Pathologist Patients Phacoemulsification Positioning Attribute Predisposition Production Property Proteins Qualifying Reactive Oxygen Species Reporting Research Residual state Resistance Resources Rest Retinal Detachment Silicones Siloxanes Structure Surface Surgical incisions Testing Underrepresented Populations Vision Visual impairment Woman Work amphiphilicity aqueous biomaterial compatibility capsule care costs cell growth design diphenyl elastomeric flexibility implantation improved improved outcome in vivo innovation lens manufacturing process medically underserved medically underserved population meetings men migration pressure prevent side effect skills standard care success

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项目摘要

ABSTRACT Cataracts, a clouding of the natural lens, is the leading cause of blindness worldwide, with a projected 40M cases by 2050. Underrepresented groups and medically underserved populations are disproportionately impacted by cataracts. Clinical treatment is limited to surgical removal of the cataractous lens, and implantation of an intraocular lens (IOL). Unfortunately, the IOL is highly susceptible to growth from residual lens epithelial cells (LECs), a complication known as posterior capsule opacification (PCO) that occurs in ~40% of adult IOL patients. Laser capsulotomy surgery is used to treat PCO, but has significant potential side effects. The proposed work will lead to the development of “LEC-resistant IOLs” based on a new amphiphilic silicone, reducing the incidence of PCO and the need for a 2nd surgery (laser capsulotomy). This work is significant given not only the expected exceptional LEC-resistance and retention of desired opto-mechanical properties of the proposed IOLs (supported by preliminary data), but also that it relies on a strategy readily integrated into existing IOL materials, designs, and manufacturing processes. Diphenyl silicones are used to prepare foldable IOLs, wherein the elastomeric nature provides the ability to fold the IOL upon implantation such that the incision size may be reduced. In this work, new amphiphilic surface-modifying additives (SMAs) [developed by the PI], comprised of a poly(ethylene oxide) (PEO) segment and siloxane tether, will be readily blended into an IOL-type diphenyl silicone. These SMAs uniquely afford rapid and substantial migration to the aqueous/biological interface to produce LEC-resistance, without impacting opto-mechanical properties. The innovation of this work rests not only in the novelty of the PI-developed SMAs, but in the departure from other strategies that have attempted to produce IOLs with resistance to LEC growth (e.g., change to IOL geometric design, complex surface treatment, and reactive oxygen species (ROS)-producing modifiers). The approach to accomplish this work relies on a systematic and robust methods, and will be led by a team of skilled experts. In Aim 1 [led by Grunlan, PI], silicone formulations will be prepared with SMAs of varying structure and concentration in the diphenyl silicone, key material properties assessed, and IOLs prepared from formulations meeting success criteria. In Aim 2 [led by Chandler, Co-I] select formulations will be evaluated for resistance to LEC growth, and select IOLs assessed ex vivo in rabbit and human eyes with a commercial silicone IOL used as a control. Following iterations of Aim 1 and 2, in Aim 3 [led by Scott, Co-I), a SMA-modified IOL will be evaluated in a rabbit model, and biocompatibility and resistance to LEC growth compared to the commercial IOL. The clinical consultant, Dr. Lee, M.D. (a comprehensive ophthalmologist and ocular pathologist) will provide guidance to these studies.

抽象的白内障是自然镜头的阴云到2050年，案件。代表性不足的群体和医疗服务不足的人群不成比例受白内障的影响。临床治疗仅限于手术去除白内障晶状体，并且人工晶状体（IOL）的植入。不幸的是，IOL非常容易受到残留的增长晶状体上皮细胞（LEC），这是一种称为后胶囊的并发症（PCO），发生在〜40％的成人IOL患者。激光囊切开术手术用于治疗PCO，但具有明显的潜在侧面效果。拟议的工作将导致基于新的两亲性的“抗lec抗IOL”的发展有机硅，减少了PCO的事件和第二手术（激光囊膜切开术）的需求。这项工作是鉴于预期的特殊LEC耐药性和所需的Optnerical的保留不仅有意义提议的IOL的属性（在初步数据的支持下），但也很容易依赖策略集成到现有的IOL材料，设计和制造过程中。二苯基有机硅用于准备可折叠的IOL，其中弹性性质提供了植入时折叠IOL的能力使切口大小可以减小。在这项工作中，新的两亲性表面修饰添加剂（SMA） [由PI开发的]，由聚（乙烷氧化物）（PEO）段和硅氧烷系绳组成混合成IOL型二苯基硅酮。这些SMA独特地实现了快速而实质性的迁移到水/生物界面可产生lec抗性，而不会影响光学特性。这这项工作的创新不仅取决于Pi开发的SMA的新颖性，而且还偏离其他试图生产具有抵抗LEC增长的IOL的策略（例如，更改为IOL 几何设计，复杂的表面处理和活性氧（ROS）产生修饰符）。完成这项工作的方法依赖于系统性和强大的方法，并将由一个团队领导熟练的专家。在AIM 1 [由Grunlan，Pi]领导，有机硅配方将使用变化的SMA制备二苯基硅酮的结构和浓度，评估的关键材料特性以及制备的IOL 符合成功标准的公式。在AIM 2中[由Chandler领导，Co-I]精选公式将是评估了对LEC生长的抗性，并选择了在兔子和人眼中评估的IOL，并具有商业硅胶IOL用作对照。在AIM 1和2的迭代之后，在AIM 3 [由Scott，Co-I领导）， SMA修饰的IOL将在兔模型中进行评估，并具有生物相容性和对LEC生长的抗性与商业IOL相比。临床顾问Lee博士，医学博士（一名全面的眼科医生眼病理学家）将为这些研究提供指导。