Biomimetic accommodating intraocular lens

The crystalline lens allows the eye to focus on near and far objects. During the aging process, it loses its ability to focus and often becomes cloudy during cataract formation. At this point, traditional medical therapy replaces the lens with an artificial replacement lens. Although replacement lenses for the crystalline lens have been implanted since 1949 for cataract surgery, none of the FDA-approved lenses mimic the anatomy of the natural lens. Hence, they are not able to focus in a manner similar to the youthful lens. Instead, they function in a manner similar to the aged lens and only provide vision at a single distance or at a very limited range of focal distances. Patients with the newest implants are often obliged to use reading glasses when using near vision, or suffer from optical aberrations, halos, or glare. Therefore, there is a need to provide youthful vision after lens surgery in terms of focusing ability, accurate optical power, and sharp focus without distortion or optical aberrations.

This thesis presents an approach to restoring youthful vision after lens replacement. An intraocular lens (IOL) that can provide accurate visual acuity along with focusing ability is proposed. This IOL relies on the natural anatomy and physiology of the eye, and therefore is actuated in a manner identical to the natural lens. In addition, the lens has the capability for adjustment during or after implantation to provide high-acuity vision throughout life.

The natural anatomy and physiology of the eye is described, along with lens replacement surgery. A lens design is proposed to address the unmet need of lens-replacement patients. Specific care in the design is made for small surgical incisions, high visual acuity, adjustable acuity over years, and the ability to focus similar to the natural lens. Methods to test the IOL using human donor tissue are developed based upon prior experiments on the ex vivo natural lens. These tools are used to demonstrate efficacy of the newly developed accommodating intraocular lens.

To further demonstrate implant feasibility, materials and processes for building the lens are evaluated for biocompatibility, endurance, repeatable manufacture, and stability. The lens biomechanics are determined after developing an artificial anatomy testing setup inspired by the natural anatomy of the human focusing mechanism. Finally, based upon a mechanical and optical knowledge of the lens, several improved lens concepts are proposed and demonstrated for efficacy.

A model of the olfactory bulb and beyond

The olfactory bulb of mammals aids in the discrimination of odors. A mathematical model based on the bulbar anatomy and electrophysiology is described. Simulations of the highly non-linear model produce a 35-60 Hz modulated activity, which is coherent across the bulb. The decision states (for the odor information) in this system can be thought of as stable cycles, rather than as point stable states typical of simpler neuro-computing models. Analysis shows that a group of coupled non-linear oscillators are responsible for the oscillatory activities. The output oscillation pattern of the bulb is determined by the odor input. The model provides a framework in which to understand the transformation between odor input and bulbar output to the olfactory cortex. This model can also be extended to other brain areas such as the hippocampus, thalamus, and neocortex, which show oscillatory neural activities. There is significant correspondence between the model behavior and observed electrophysiology.

It has also been suggested that the olfactory bulb, the first processing center after the sensory cells in the olfactory pathway, plays a role in olfactory adaptation, odor sensitivity enhancement by motivation, and other olfactory psychophysical phenomena. The input from the higher olfactory centers to the inhibitory cells in the bulb are shown to be able to modulate the response, and thus the sensitivity, of the bulb to odor input. It follows that the bulb can decrease its sensitivity to a pre-existing and detected odor (adaptation) while remaining sensitive to new odors, or can increase its sensitivity to discover interesting new odors. Other olfactory psychophysical phenomena such as cross-adaptation are also discussed.