Cornea and Lens Research
Corneal Wound Healing
Corneal scarring is a major cause of decreased visual quality and vision loss worldwide. Causes of corneal scarring include almost any disruption to normal corneal structure and function, whether from infection, corneal surgery, corneal transplantation, ocular trauma (chemical or physical) or corneal dystrophies. There is no suitable means of controlling corneal scaring despite more than 25 years trying to characterize cytokine signaling during wound healing. Our ultimate goal is to understand mechanisms of corneal wound healing and to design effective therapies to treat or prevent corneal scarring.
Molecular manipulation of corneal wound healing
Drs. Krystel Huxlin, Holly Hindman, Richard Phipps and Patricia Sime have worked together to investigate a relative newcomer in the field of corneal pharmacologics: PPARγ ligands. PPARγ is a nuclear receptor/transcription factor, whose ligands are beginning to emerge as central elements in attenuation of inflammation and fibrosis in other body tissues. However, though highly promising, the role and mechanisms of action of PPARγ ligands as natural modulators of fibrosis in the cornea remain unexplored. Current clinical approaches to reduce corneal fibrosis are only partially effective and carry significant side effects, while PPARγ ligands are already clinically available as “insulin sensitizers” for diabetes. Therefore, the translational potential of our work is very high. Ongoing studies use both in vitro (cell culture) and in vivo (in animal models) approaches to define the relative effectiveness and mechanisms of action of PPARγ ligands in the unique environment of corneal wounds. This line of work suggests that we can pharmacologically control different aspects of corneal wound healing by acting on different intracellular pathways within corneal keratocytes, epithelial and immune cells. The uniqueness of our approach is that we can not only manipulate biological and molecular aspects of corneal fibrosis, but also measure their optical consequences in vivo. Ultimately, what we are looking for is a treatment for fibrosis that preserves and restores the cornea’s structure, function and optical properties. We hope that this work will provide significant, meaningful new information that will have a major impact on the treatment of many types of corneal scarring in humans.
A corneal transplant also known as a corneal graft or keratoplasty is a surgical procedure that replaces the scarred or diseased cornea with clear corneal tissue from a donor. The Flaum Eye Institute is one of a limited number of centers nationally that is conducting clinical trials with the newest forms of keratoplasty. Holly Hindman, M.D., M.P.H. is heading up this area of clinical research. For the past 40 years, corneal transplantation has involved replacing the central cornea in partial thickness transplants or full thickness penetrating keratoplasty. While highly successful, these procedures also present some problems for patients. Healing is a slow process with sutures often left in place for a year or more, raising the risk of infection and rejection. Most patients will also experience astigmatism at a rate significantly higher than people with healthy eyes. Over time, surgeons and researchers have learned that most diseased corneas are diseased only in the back layer, paving the way to posterior lamellar keratoplasty. In this revolutionary procedure, with just a small side incision, only the diseased back layer is replaced, about 20 percent of the cornea. Early results show that this new technology allows patients to heal faster with less risk of rejection and less astigmatism. Like other physicians and scientists throughout the Eye Institute, these researchers are moving toward a more global view of their specialty area—leveraging distinct perspectives to preserve and enhance vision for their patients and for future generations.
Advanced anterior segment imaging and development of customized vision correction
Drs. Geunyoung Yoon, Scott MacRae and James Aquavella study the optical properties of the highly aberrated corneas of patients with corneal diseases such as keratoconus, and are developing methods to treat those disorders. Dr. Yoon is also developing methods to adapt the methods of wavefront sensing to the manufacture of contact lenses that can provide customized correction of high order refractive errors. Drs. James Zavislan, Jannick Rolland and James Aquavella are measuring the optical properties of the tear film, with the goal of developing methods for the amelioration of tear film abnormalities such as dry eye. This group uses wave front sensing, optical coherence tomography (OCT) and polarimetry to make these measurements. Applications of the advanced imaging technologies developed at the Flaum Eye Institute have wide-ranging application, including for the study and correction of:
Corneal pathologies/ injuries/ surgeries
Accommodation and presbyopia
Intra-tissue Refractive Index Shaping (IRIS) for non-invasive refractive correction
IRIS is a process invented at the University of Rochester by a team of scientists under the leadership of Drs. Krystel Huxlin, Wayne Knox and Jonathan Ellis, who demonstrated that it was possible to use a low-energy, high-repetition rate femtosecond laser to alter the refractive index of transparent, living tissues (such as the cornea and lens) without causing massive amounts of tissue damage or inducing a wound healing and scarring response. Our long-term goal with this research is to develop the use of femtosecond micromachining as a non-damaging method of customizing the refractive correction in a human eye, be it in the cornea, lens or implanted IOLs. Current experiments are first testing and developing this technology in animal models, with specific projects including:
assessing the durability of inscribed femto-IRIS patterns in a living cornea over time,
assessing the biological reaction and especially, the presence or absence of a corneal wound healing reaction to an inscribed femto-IRIS pattern in a living cornea over time,
assessing the wavefront aberration and biomechanical changes induced by IRIS patterns over time.