Defense Date


Document Type


Degree Name

Doctor of Philosophy


Biomedical Engineering

First Advisor

Ilko K. Ilev, Ph.D.

Second Advisor

Gerald Miller, Ph.D.

Third Advisor

Esen Akpek, M.D.

Fourth Advisor

Paul Wetzel, Ph.D.

Fifth Advisor

Daniel Conway, Ph.D.


One of the most recent advancements in laser technology is the development of ultrashort pulsed femtosecond lasers (FSLs). FSLs are improving many fields due to their unique extreme precision, low energy and ablation characteristics. In the area of laser medicine, ophthalmic surgeries have seen very promising developments. Some of the most commonly performed surgical operations in the world, including laser-assisted in-situ keratomileusis (LASIK), lens replacement (cataract surgery), and keratoplasty (cornea transplant), now employ FSLs for their unique abilities that lead to improved clinical outcome and patient satisfaction.

The application of FSLs in medical therapeutics is a recent development, and although they offer many benefits, FSLs also stimulate nonlinear optical effects (NOEs), many of which were insignificant with previously developed lasers. NOEs can change the laser characteristics during propagation through a medium, which can subsequently introduce unique safety concerns for the surrounding tissues. Traditional approaches for characterizing optical effects, laser performance, safety and efficacy do not properly account for NOEs, and there remains a lack of data that describe NOEs in clinically relevant procedures and tissues. As FSL technology continues to expand towards new applications, FSL induced NOEs need to be better understood in order to ensure safety as FSL medical devices and applications continue to evolve at a rapid pace.

In order to improve the understanding of FSL-tissue interactions related to NOEs stimulated during laser beam propagation though corneal tissue, research investigations were conducted to evaluate corneal optical properties and determine how corneal tissue properties including corneal layer, collagen orientation and collagen crosslinking, and laser parameters including pulse energy, repetition rate and numerical aperture affect second and third-harmonic generation (HG) intensity, duration and efficiency. The results of these studies revealed that all laser parameters and tissue properties had a substantial influence on HG. The dynamic relationship between optical breakdown and HG was responsible for many observed changes in HG metrics. The results also demonstrated that the new generation of therapeutic FSLs has the potential to generate hazardous effects if not carefully controlled. Finally, recommendations are made to optimize current and guide future FSL applications.


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