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)

• 批准号: 10841859
• 负责人: Melissa Grunlan
• 金额: $ 7.82万
• 依托单位: TEXAS ENGINEERING EXPERIMENT STATION
• 依托单位国家: 美国
• 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/10841859
• 关键词: Adult; Biological; Blindness; Cataract; Cataract Extraction; Clinical; Clinical Treatment; Complex; Complication; Data; Doctor of Medicine; Elastomers; Epithelial Cells; Ethylene Oxide; Excision; Eye; Formulation; Growth; Human; Incidence; Intraocular Lens Implantation; Intraocular lens implant device; Lasers; Lens development; Methods; Modeling; Nature; Operative Surgical Procedures; Ophthalmologist; Oryctolagus cuniculus; Outcome; Pathologist; Patients; Predisposition; Property; Reactive Oxygen Species; Residual state; Resistance; Rest; Silicones; Siloxanes; Structure; Surface; Surgical incisions; Underrepresented Populations; Vision; Work; amphiphilicity; aqueous; biomaterial compatibility; capsule; cell growth; design; diphenyl; elastomeric; implantation; improved; improved outcome; innovation; lens; manufacturing process; medically underserved population; meetings; migration; side effect; skills; success

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。