Collaborative: Analysis of Mechanical Properties and Thermal Effects of Cornea Following Femtosecond Laser Intrastromal Refractive Surgery

CBET-0827473 Guo激光矫正屈光不正手术于1996年被FDA批准，已进行了数百万次手术。当手术开始时，它被称为激光屈光性角膜切削术(PRK)，在准分子激光消融以矫正角膜形状之前，先机械地刮去角膜外层上皮。机械地去除上皮会导致眼表疼痛一天左右，直到表面愈合。PRK很快被激光辅助原位角膜磨镶术(LASIK)所取代，在LASIK中，一种名为角膜刀的设备被用来在角膜表面以下150-200微米处制造一块瓣。当准分子激光消融角膜表面以形成正确的表面，然后将其放回原位时，该瓣被折叠起来。薄皮瓣的所有上皮细胞完好无损，与新的表面相符，对患者来说痛苦较少。然而，该瓣带来了新的并发症，如游离角膜瓣、上皮细胞生长不良、瓣滑脱或无意中的眼内穿孔。尽管LASIK已经在大量患者中获得了成功，但并发症较少的新技术仍然是令人向往的。智能优点：飞秒基质内消融通过消除LASIK手术中所需的“瓣”，将极大地改进角膜屈光手术。该项目的目标集中在使用飞秒激光进行角膜消融的基础热和力学分析，这对安全性和有效性评估至关重要。在角膜腔内产生的消融产品是什么？消融过程中积聚的温度和压力如何？消融过程对残留的角膜组织有何影响？压力或温度会削弱角膜吗？它会有可能导致角膜恶化或阻止进一步矫正屈光不正的长期影响吗？激光诱导击穿的机理是什么？主要的研究任务是(A)最佳激光参数的实验测试，(B)晶状体的光学和机械性质的分析，(C)了解角膜消融过程中的消融特征和热影响区的确定，以及(D)确定飞秒激光角膜基质内消融的长期风险。实验将在从屠宰场获得的动物眼睛和从眼库获得的人(身体)眼睛上进行，并将安装在装有加压水溶液的夹具中。使用兔眼的活体实验也被考虑在内。更广泛的影响：除了实现科学目标之外，这一合作项目还将极大地促进整合调查人员的教育和研究活动，并加强校外合作。教育目标是让研究生在各自学习曲线的早期阶段参与有意义的、亲身实践的科学实验工作。这项研究的结果将被记录在万维网上，以促进与其他科学家和医生的积极合作。这项研究的结果将通过学生的会议演讲和发表期刊文章来传播。因此，这项研究将产生高质量的研究生学位论文，以及为本科生的高年级设计项目。通过这项研究获得的结果将有助于为开发一门新的课程准备材料，并为教育学生、FDA员工、眼科医生和有兴趣了解飞秒基质内角膜切削术的研究人员举办研讨会。这项工作的潜在变革性：使用飞秒激光的间质内光学手术可能提供激光手术所提供的最准确的屈光矫正。当脉冲与热扩散时间相比非常短时，需要保存的附近组织几乎没有加热。此外，消融需要切除的组织所需的时间更短。这减少了烧蚀过程中气泡的形成，并减少了热扩散造成的损害。因此，它可以通过聚焦上皮在角膜表面下的基质材料中雕刻一个矫正透镜(或小晶状体)来完成消融。这种方法消除了皮瓣，并可能消除任何可能需要扭曲缝合的切开。然而，在这种飞秒激光手术获得批准之前，它的安全性应该得到证实。到目前为止，飞秒间质内屈光手术的并发症还没有被太多地探讨，将通过这项研究来解决。

CBET-0827473GuoLaser surgery to correct refractive error was approved by the FDA in 1996 and has been performed millions of times. When the procedure began it was known as photo-refractive keratectomy (PRK) where the outer cornea epithelium is scraped off mechanically prior to excimer laser ablation to correct the corneal shape. Mechanically removing the epithelium resulted in painful eye surfaces for a day or so until the surface healed. PRK was soon supplanted by laser assisted in-situ keratomilusis (LASIK) in which a device known as a keratome was used to create a flap that is 150-200 micrometers below the surface of the cornea. This flap is folded out of the way while the excimer laser ablates the corneal surface to form the correct surface and is then put back in place. The thin flap has all of its epithelium intact, conforms to the new surface and is less painful to the patient. However, the flap brings new complications such as a free corneal flap, epithelial down-growth, flap slippage or inadvertent intraocular perforation. Although LASIK has been successful for a large number of people, newer techniques with fewer complications are still desirable. Intellectual Merit: Femtosecond intrastromal ablation will drastically improve corneal refractive surgery by eliminating the "flap" necessary in LASIK surgery.The goal of this project is focused on fundamental thermal and mechanical analysis of corneal ablation using femtosecond lasers which is critical for safety and efficacy evaluation. What are the ablative products that are created inside the corneal cavity? How about the temperature and pressure that builds up during ablation? How does the ablation process affect the corneal tissue that remains? Can the pressure or temperature weaken the cornea? Can it have long term effects that could cause deterioration of the cornea or prevent further correction of the refractive error? What is the mechanism of laser induced breakdown? The major research tasks are (a) experimental test of optimal laser parameters, (b) analysis of optical and mechanical properties of the lenticles, (c) understanding the ablation characteristics and determination of heat affected zone during corneal ablation, and (d) determination of the long term risks of femtosecond intrastromal ablation of cornea. Experiments will be performed on animal eyes obtained from slaughter houses and human (cadaver) eyes obtained from eye banks and will be mounted into a fixture complete with pressurized aqueous fluid. In vivo experiments using rabbit eyes are also considered. Broader Impact: In addition to meeting the scientific goals, this collaborative project will contribute significantly to integrate the education and research activities of the investigators and enhance extramural collaborations. The educational objective is to involve graduate students in meaningful, hands-on scientific experimental work at an earlier stage of their respective learning curve. The results of this research will be documented, as available, on the World Wide Web to promote active collaborations with other scientists and doctors. The results of this research will be disseminated through conference presentations by students as well as publication of journal articles. This research will thus result in production of high quality dissertations for graduate students, as well as senior year design projects for undergraduate students. The results obtained through this research will help to prepare materials for developing a new course and to conduct workshops for educating students, FDA employees, ophthalmologists, and researchers interested in learning about concerns of femtosecond intrastromal corneal ablation. Potentially Transformative Nature of the Work: Intrastromal optical surgery using femtosecond lasers potentially offers the most accurate refractive correction that laser surgery has to offer. When pulses are very short compared to the thermal diffusion time, there is little heating of nearby tissue that needs to be preserved. Also, it takes less time to ablate away tissue that needs to be removed. This reduces gas bubble formation during ablation and lessens damage from heat diffusion. Thus it allows the ablation to be done by focusing through the epithelium to carve a correction lens (or lenticle) in the stromal material beneath the corneal surface. This method eliminates the flap and may eliminate any incision that will require potentially distorting sutures. However, before this femtosecond laser procedure is approved, its safety should be established. So far the complications of femtosecond intrastromal refractive surgery have not been explored very much and will be addressed through this research.