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

激光矫正屈光不正手术于1996年获得美国食品药品监督管理局（FDA）批准，至今已进行了数百万次。当手术开始时，它被称为光屈光性角膜切除术（PRK），在准分子激光消融之前，机械刮掉角膜外上皮，以纠正角膜形状。机械移除上皮细胞会导致眼睛表面疼痛一天左右，直到表面愈合。PRK很快被激光辅助原位角膜磨圆术（LASIK）所取代，在LASIK中，一种被称为角膜瓣的装置被用来在角膜表面以下150-200微米处创建一个皮瓣。当准分子激光消融角膜表面形成正确的表面时，这个皮瓣被折叠起来，然后被放回原位。薄皮瓣的所有上皮都完好无损，符合新表面，对患者的痛苦较小。然而，角膜瓣也带来了新的并发症，如游离角膜瓣、上皮向下生长、角膜瓣滑脱或无意的眼内穿孔。虽然LASIK手术对很多人来说是成功的，但更少并发症的新技术仍然是可取的。知识优势：飞秒星间消融通过消除LASIK手术中必需的“皮瓣”，将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的基本热力学分析，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物是什么？那消融过程中产生的温度和压力呢？消融过程如何影响剩余的角膜组织？压力或温度会使角膜变弱吗？它是否有长期的影响，可能导致角膜恶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？主要研究任务是(a)最佳激光参数的实验测试，(b)晶状体光学和力学特性的分析，(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。实验将在从屠宰场获得的动物眼睛和从眼库获得的人类（尸体）眼睛上进行，并将安装在装有加压水流体的固定装置中。还考虑了兔眼的体内实验。更广泛的影响：除了达到科学目标外，该合作项目将对整合研究人员的教育和研究活动以及加强校外合作做出重大贡献。教育目标是让研究生在他们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可用的情况下被记录在万维网上，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在会议上的演讲和期刊文章的发表来传播。这项研究将为研究生提供高质量的论文，并为本科生提供大四的设计项目。通过这项研究获得的结果将有助于准备开发新课程的材料，并为学生、FDA员工、眼科医生和有兴趣了解飞秒角膜上皮内消融问题的研究人员举办研讨会。潜在的变革性工作：使用飞秒激光的眼内光学手术可能提供激光手术所能提供的最精确的屈光矫正。当脉冲与热扩散时间相比非常短时，需要保存的附近组织很少受热。此外，它需要更少的时间来消融需要移除的组织。这减少了烧蚀过程中气泡的形成，减少了热扩散造成的损害。因此，它允许消融通过聚焦通过上皮在角膜表面下的基质材料雕刻一个矫正晶状体（或透镜）来完成。这种方法可以消除皮瓣，也可以消除任何需要潜在扭曲缝合线的切口。然而，在这个飞秒激光程序被批准之前，它的安全性应该被确定。到目前为止，飞秒角膜内屈光手术的并发症还没有得到很好的探讨，将通过本研究来解决。

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.