AEVR Hosts First-ever World Keratoconus Day Congressional Briefing Featuring Research into Novel Treatments

 

Left to right: Briefing faculty included research speaker Dimitrios Karamichos, PhD (Dean McGee Eye Institute/University of Oklahoma), National Keratoconus Foundation Executive Director Mary Prudden, JD, and patient advocate Rachel Dungan, MSSP

On November 7, in recognition of the second annual World Keratoconus Day 2017 (held on November 10), AEVR’s Decade of Vision 2010-2020 Initiative and co-sponsors (see box below) held a Congressional Briefing entitled Spearheading Keratoconus Research: A Quest for Novel Treatments that focused on Keratoconus (KC), a degenerative disease where the clear covering of the eye—the cornea—thins or bulges, leading to scarring and blurred or distorted vision. This is a disease that, while it does not result in irreversible blindness, can cause severe disability and functional blindness.

Mary Prudden, JD, National Keratoconus Foundation (NKCF) Executive Director, provided a welcome and perspective on KC, which is not a rare disease. With improved testing, it now appears that the prevalence—from most-mild to the most-extreme—is 1 in every 400 individuals. Although certain ethnic groups seem to have a higher incidence, especially those from India, Pakistan, Turkey and the Middle East, every nationality and both sexes are equally affected. Although no specific event causes KC to develop, researchers believe certain eyes have a biomechanical weakness, a slight anatomical difference, or a genetic predisposition that, when combined with environmental factors, results in the disease. In most cases, there is no family history of the condition. It is usually diagnosed in the late-teen and early-adult years, which a critical time in life where individuals begin their careers or complete their education and where vision dramatically deteriorates and their ability to function is compromised.

Although there is no cure for KC, patients with mild cases can be treated with rigid gas permeable lenses or scleral contact lenses. As the disease progresses, contact lenses cannot compensate for the changes to the cornea, and become ineffective or too painful to tolerate. Until recently, a corneal transplant had been recommended, and KC patients have been the most frequent recipients of corneal transplants. But this an invasive surgical procedure. In 2016, the Food and Drug Administration (FDA) approved corneal crosslinking, which is a non-invasive procedure that involves applying liquid riboflavin (Vitamin B2) eye drops, followed by a controlled application of ultraviolet light to strengthen the corneal collagen. This procedure is now recommended for newly diagnosed patients as a method to halt or slow disease progression. National Eye Institute (NEI) funding has been important in the development of these various treatments.

NEI-funded researcher Dimitrios Karamichos, PhD, an Associate Professor of Ophthalmology and Cell Biology at the Dean McGee Eye Institute at the University of Oklahoma, reiterated that KC is a complex disease of the cornea associated with various genetic, environmental, and exogenous—or external—factors. Despite significant advancements, the pathophysiology of KC remains poorly understood. Although there are a large number of studies using human corneal cells isolated from KC donors, these have failed to initiate under laboratory conditions the development of KC, since it is difficult to fully determine the critical cellular and molecular contributors to the disease or to vary them independently in a non-physiologically relevant model. Dr. Karamichos announced that, in 2012, his laboratory was the first to introduce a human 3-dimensional model for KC—an approach that is more translational and able to mirror what is seen in KC patients. It has since facilitated the study of KC and to promote the development of novel therapeutics via high-throughput analysis.

He recognized that, despite these advancements and discoveries, therapeutic approaches developed in the lab have to be validated with human studies and/or clinical trials. The lack of an animal model has also severely hampered progress in KC studies. These limitations are another reason that key molecular mechanisms responsible for disease onset and progression have not been identified. In order to overcome such limitations, researchers have turned to human samples and biological fluids. Classically, the tear film has been analyzed because it is in direct contact with the tissue affected—the cornea. Although these studies have revealed modulation of several factors, most of these observations are from specific or subset populations and a specific time point, which clouds the determination of a causal relationship between altered proteins or cytokines (proteins that affect interaction or communication between cells) and KC onset or progression. Similar limitations exist in studies analyzing patient’s blood samples using sophisticated genetic techniques. A number of genes have been reported as candidates for KC—and some have been linked to a small percentage of cases—but genetic studies to-date have been generally inconclusive.

Dr. Karamichos noted that, as of 2016, his laboratory reported the first comprehensive study showing the diagnostic potential of human saliva samples and highlighted the role of sex hormones in KC onset and progression. Saliva sampling had not been previously analyzed in KC patients despite the fact it is a noninvasive bodily fluid that has provided clinical clues to diseases such as cancer and diabetes. Most of the compounds found in blood are also present in saliva, giving rise to the notion that saliva is a mirror of the blood. Saliva appears to be the ideal source for clinical trials and the diagnosis of KC. His laboratory is currently correlating data collected from both laboratory experiments and human studies in order to enable new insights into a broad variety of KC disease mechanisms, as well as to provide a test bed for screening new therapies. The ultimate goal is to identify therapeutic targets for disease prevention and early diagnosis, thus delaying or arresting its progression and improving treatment.

Patient advocate Rachel Dungan, MSSP, spoke about how the onset of the disease in her college years severely affected her career and educational plans—as well as her mental health— as she dealt with obscured night vision, difficulty reading faces, limited awareness of surroundings, minimized depth perception, and persistent discomfort. She has worked with five different specialists who have created more than 85 distinct sets of customized corrective lenses in an effort to produce a pair that enhances vision while mitigating the pain of wearing hard contact lenses. Since winning the NKCF Short Film Festival in which she described her life with KC, she has served as an active patient advocate, speaking at conferences hosted by ARVO and the University of California-Davis Eye Research Institute. In that capacity, she observed the significant impact on quality of life from KC stating that, “Almost every patient I meet admits—often emotionally—to compromising on social engagement or professional advancement due to the challenges of living with this condition.”

From left: AEVR Briefing co-sponsors ARVO and Eye Bank Association of America, represented by Iris Rush and Kevin Corcoran/Jennifer DeMatteo, respectively, with Scott Haber (American Academy of Ophthalmology)

NKCF Executive Director Mary Prudden with Charles McCoy, from the office of Cong. Keith Rothfus (R-PA)