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

CBET-0827473 Guo激光手术矫正屈光不正于1996年获得FDA批准，并已进行了数百万次。当手术开始时，它被称为屈光性角膜切除术（photo-refractive keratectomy，简称PRK），其中在准分子激光消融之前机械地刮除外角膜上皮以矫正角膜形状。机械去除上皮导致眼睛表面疼痛一天左右，直到表面愈合。激光辅助原位角膜磨镶术（LASIK）很快取代了角膜磨镶术，其中使用称为角膜刀的设备来创建角膜表面以下150-200微米的瓣。当准分子激光消融角膜表面以形成正确的表面时，将该瓣折叠出来，然后放回原位。薄皮瓣的所有上皮完整，符合新的表面，并减少病人的痛苦。然而，该瓣带来了新的并发症，如游离角膜瓣、上皮向下生长、瓣滑动或无意中的眼内穿孔。虽然LASIK已经成功地为许多人，较新的技术与较少的并发症仍然是可取的。智力优势：飞秒激光角膜基质内消融术将通过消除LASIK手术中所需的“瓣”而大大改善角膜屈光手术。本项目的目标是对飞秒激光角膜消融术进行基本的热和力学分析，这对于评估安全性和有效性至关重要。角膜腔内产生的消融产品有哪些？消融过程中产生的温度和压力如何？消融过程如何影响残留的角膜组织？压力或温度会削弱角膜吗？它是否有长期影响，可能导致角膜退化或阻止进一步矫正屈光不正？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）分析角膜基质的光学和机械特性，（c）了解角膜消融过程中的消融特性和热影响区的确定，以及（d）确定飞秒角膜基质内消融的长期风险。将对从屠宰场获得的动物眼睛和从眼库获得的人（尸体）眼睛进行实验，并将其安装到装有加压水性流体的夹具中。还考虑了使用兔眼的体内实验。更广泛的影响：除了满足科学目标，这一合作项目将大大有助于整合研究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，动手的科学实验工作。这项研究的结果将在万维网上记录，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报告以及期刊文章的出版来传播。因此，这项研究将导致生产高质量的论文研究生，以及高年级设计项目的本科生。通过本研究获得的结果将有助于为开发新课程准备材料，并为教育学生、FDA员工、眼科医生和有兴趣了解飞秒角膜基质内消融问题的研究人员举办研讨会。工作的潜在变革性质：使用飞秒激光的基质内光学手术可能提供激光手术所能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，几乎没有需要保留的附近组织的加热。而且，消融需要切除的组织所需的时间更少。这减少了消融期间的气泡形成，并减少了热扩散造成的损害。因此，它允许通过聚焦穿过上皮以在角膜表面下方的基质材料中雕刻矫正透镜（或透镜体）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口。然而，在这种飞秒激光手术获得批准之前，应该确定其安全性。到目前为止，飞秒基质内屈光手术的并发症还没有得到很大的探讨，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.