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

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.

抽象的白内障是一种自然晶状体混浊的疾病，是全世界导致失明的主要原因，预计有 4000 万到 2050 年，代表性不足的群体和医疗服务不足的人口比例不成比例受白内障影响的临床治疗仅限于手术切除白内障晶状体，以及不幸的是，人工晶状体很容易因残留物而生长。晶状体上皮细胞（LEC），一种称为后囊混浊（PCO）的并发症，发生在约 40% 的成人 IOL 患者采用激光囊切开术治疗 PCO，但具有显着的潜在副作用。拟议的工作将导致基于新型两亲性物质的“抗 LEC IOL”的开发。硅胶，减少 PCO 的发生率和第二次手术（激光囊切开术）的需要。不仅考虑到预期的出色的 LEC 抗性和所需光机械的保留，这一点也很重要所提出的 IOL 的特性（由初步数据支持），而且它很容易依赖于策略将现有的人工晶状体材料、设计和制造工艺集成到一起。制备可折叠人工晶状体，弹性体性质提供了植入时折叠人工晶状体的能力在这项工作中，新的两亲性表面改性添加剂（SMA）可以减小切口尺寸。 [由 PI 开发]由聚环氧乙烷 (PEO) 链段和硅氧烷系链组成，将很容易获得这些 SMA 混合到 IOL 型二苯基硅酮中，具有独特的快速且大量的迁移能力。水/生物界面产生 LEC 抗性，而不影响光机械性能。这项工作的创新不仅在于 PI 开发的 SMA 的新颖性，而且在于与尝试生产抗 LEC 生长的 IOL 的其他策略（例如，改变 IOL 几何设计、复杂的表面处理和产生活性氧 (ROS) 的改性剂）。完成这项工作的方法依赖于系统和稳健的方法，并将由一个团队领导在目标 1 [由 PI Grunlan 领导] 中，将使用不同的 SMA 来制备有机硅配方。二苯基硅酮的结构和浓度、关键材料特性评估以及人工晶状体的制备在目标 2 [由 Chandler, Co-I 领导] 中，将选择符合成功标准的配方。评估对 LEC 生长的抵抗力，并使用 IOL 在兔子和人眼中进行离体评估在目标 3 [由 Scott, Co-I 领导] 中，使用商业硅 IOL 作为对照。将在兔子模型中评估 SMA 改良的 IOL，以及生物相容性和对 LEC 生长的抵抗力与商业IOL相比。临床顾问Dr. Lee, M.D.（综合眼科医生）和眼病理学家）将为这些研究提供指导。