Femtosecond Laser Processing of Ophthalmic Materials and Ocular Tissues: A Novel Approach for Non-invasive Vision Correction.

摘要

The goal of this thesis is to demonstrate a novel approach for non-invasive customized vision correction. Endeavors targeted at this goal are exhibited in two aspects: femtosecond laser micromachining in ophthalmic hydrogel polymers (for application to customized IOL - intraocular lens or contact lenses), and Intra-tissue Refractive Index Shaping (IRIS) (for application to non-invasive corneal refractive surgery). Femtosecond laser micromachining has been widely used for its three- dimensional structuring capability. In the application to ophthalmic hydrogel polymers, we found a refractive index change up to +0.06, which is much larger than that obtained in glasses. The first half of this thesis investigates femtosecond laser micromachining in bio-compatible, FDA-approved ophthalmic polymers, which are used for IOL materials. While large refractive index changes could be achieved in undoped hydrogel polymers, they were attained only at extremely slow scanning speeds. However, we found that doping with a two-photon sensitizer in the polymer materials could greatly enhance the efficiency, resulting in more than 1000X faster scanning speeds as well as larger refractive index changes. This made our technique much more favorable for clinical applicability. Optimization of the polymer materials and the doping contents reached a conclusion of the best material and doping choice, which yielded the largest attainable refractive index change with a wide writing dynamic range - from no change in the material to the point where optical damage occurs in the hydrogel polymers. This material is AkreosRTM doped with 2% X-monomer. We then performed a calibration of the refractive index change versus the scanning speed at certain experimental parameters in this Akreos material. A large amount of effort was devoted to look for the best form of refractive structure to write into the polymer for vision correction. With optical modeling and experimental implementation, we were able to design and write a cylindrical lens, measured with cylindrical power up to one diopter. The second half of this thesis presents the application of femtosecond laser micromachining to corneal refractive surgery, which we termed Intra-tissue Refractive Index Shaping (IRIS). Different from all existing corneal surgical procedures, our IRIS technique is a minimally invasive refractive correction procedure, which only alters the refractive index of the corneal stroma without causing cell death or inducing a wound healing response. Similar to the case of hydrogel polymers, we found that, by doping with two-photon enhancers (sodium fluorescein, Na-Fl) to the corneal tissue, both the refractive index change and the scanning speeds were greatly increased from previous demonstration in fixed corneal tissue. This form of IRIS was termed NIR-IRIS, using near-infrared femtosecond lasers. However, due to the complication of doping Na-Fl into the cornea in clinical settings, we recently developed another form of IRIS, termed as Blue-IRIS, using blue femtosecond laser pulses around 400 nm wavelength. Using the endogenous two-photon absorption (TPA) in native, undoped, live cornea, we were able to achieve even larger refractive index change (up to ~0.037) at much faster scanning speeds. No substantial cell death or wound healing response was induced. We used live cat cornea for validating and testing the IRIS technique. As a completely different scenario from the corneal tissue, it is much more difficult to perform the IRIS procedure in the live cat cornea. Finally, we designed a customized suction ring to applanate the cornea when focusing the laser beam into the cornea, which has greatly improved the optical quality of structures written in vivo. Recently, we designed and implemented a custom-built shaker-scanning system, which rendered much more uniform refractive index change without the random errors present in the three-dimensional servo-stage scanning system. Integration of this newly designed shaker-scanning system has produced more than two diopters of astigmatism in the live cat cornea, lasting for at least one month to date. In short, this thesis investigated the application of femtosecond lasers towards the goal of non-invasive customized vision correction, in terms of both customized intraocular lenses (IOLs) and corneal refractive correction. In vivo studies using live animal models have validated the feasibility of this technique in the short term.