Novel Treatment for Post-LASIK Ectasia

DESCRIPTION (provided by applicant): Of the 1.4 million refractive surgeries performed each year using laser assisted in situ keratomileusis (LASIK) in the U.S., 1 in 2500 will result in post-LASIK ectasia-a thinning and bulging of the cornea analogous to keratoconus that becomes evident months or years after the LASIK procedure. Studies of patients who developed post-LASIK ectasia have led to a risk stratification system that uses preoperative information to evaluate the risk of developing post-LASIK ectasia. Approximately 1/3 of patients satisfy the conditions that correlate with developing post-LASIK ectasia. If a treatment were available with sufficiently low cost, low risk and high efficacy, patients in the at risk group might be treated prophylactically to greatly reduce the probability of subsequent ectasia. Some cases of post-LASIK ectasia occur in patients who have preoperative profiles that would not be identified as at risk; therefore, a safe and effective means to arrest the progression of ectasia as soon as it is identified is also needed. Corneal crosslinking using the riboflavin/UVA protocol pioneered by Wollensak, Seiler, and Spoerl, has shown promise in halting the progress of post-LASIK ectasia, providing a potential treatment to postpone or avoid corneal transpantation necessitated by the ectasia. However, the treatment is costly (requiring a surgeon to perform the 35 minute procedure), painful (requiring that the cornea be debrided) and toxic (the treatment kills all cells in the anterior 300 ltm of the cornea; in the event that the cornea has already thinned to lt400 ltm, the treatment can permanently damage the endothelium). A proprietary treatment developed through collaboration of Visdex, Caltech, and UCSF successfully stabilizes corneal shape in vitro using visible light to activate Eosin Y. In relation to application as a prophylactic or a treatment for post-LASIK ectasia, the treatment would consist of lifting the LASIK flap, applying a drop of a drug to the surface of the stromal bed, closing the LASIK flap, allowing the drug to diffuse into the tissue (ca. 10 min) and then irradiating the cornea with visible light for 5 min. The treatment uses compounds that have been approved by the FDA for use in patients. Initial in-vivo experiments in rabbits indicate that the drug and irradiation are well tolerated by the eye. The objective of this Phase I STTR project is to demonstrate that such a treatment can be translated into a clinically meaningful protocol that shows efficacy in vitro matching that of the riboflavin/UVA treatment and shows safety in vivo, in contrast to the apoptosis and edema caused by riboflavin/UVA. First, in vitro experiments will optimize the Eosin Y formulation and delivery vehicles for administration under a LASIK flap, and will optimize the light delivery device to reduce treatment time and minimize retinal light exposure (Aim 1). Second, efficacy will be evaluated in vitro, testing and further optimizing the Eosin Y formulation and annular irradiation device to stabilize corneal shape after creating LASIK flaps in enucleated animal eyes (Aim 2). Finally, safety and efficacy will be evaluated in vivo using a rabbit model with the optimized Eosin Y formulation and irradiation device developed in Aims #1 and #2. By demonstrating in-vitro efficacy and in-vivo biocompatibility, this Phase I project will advance the innovative visible light activated treatment toward clinical application. Specifically, this study would set the stage for a Phase II study that would evaluate mechanical stability in human donor eyes and extend toxicity tests needed before human clinical trials. PUBLIC HEALTH RELEVANCE: Post-laser in situ keratomileusis (LASIK) ectasia is a serious complication of refractive corneal procedures resulting in progressive steepening and thinning of the cornea that can lead to severe visual loss and require corneal transplantation. This project will result in an innovative light-activated treatment that will arrest post-LASIK ectasia for those who already developed it and will serve as a preventative measure for others who are receiving the refractive correction procedure.