Top Doctors Awarded
Seven doctors from the Department of Ophthalmology and Visual Sciences were named to the 2015-16 Best Doctors in America List in adult and pediatric ophthalmology categories. Barbara Blodi, MD, Gregg Heatley, MD, MMM, Mark Lucarelli, MD, and Neal Barney, MD were named on the list in adult sub-specialties, along with Yasmin Bradfield, MD, Burton Kushner, MD and Terri Young, MD, MBA in the pediatric sub-specialty category. They join nearly 200 other UW Health physicians who are listed.
Department Hosts Inaugural Spring Science Symposium
Dale Gregerson, PhD, from the University of Minnesota School of Medicine, was the keynote speaker for a successful Spring Vision Science Research Symposium sponsored by the Department of Ophthalmology and Visual Sciences. The April 1 event, which featured talks by more than 20 researchers.
Presenters from the University of Wisconsin School of Medicine and Public Health, The Medical College of Wisconsin, University of Iowa, Northwestern University, and the University of Minnesota shared research in four main areas: Epidemiology, Retinal Disease, Glaucoma and Optic Nerve and Inflammation.
The 2015 Spring Vision Science Research Symposium was supported by the Department of Ophthalmology and Visual Sciences Dr. George K. Kambara Ophthalmology Education Fund.
Dr. Umang Mathur Brings International Ophthalmology Collaboration to Department
Dr. Umang Mathur, Medical Director of the Dr. Shroff’s Charity Eye Hospital, in New Delhi, India visited the University of Wisconsin Department of Ophthalmology and Visual Sciences in May 2016. During his Grand Rounds lecture he spoke of the special challenges in the delivery of eye care in India. Eighteen million citizens are blind, 27-30 million have low vision, yet 80% of blindness in his country is curable or preventable. “The irony is that international patients are flocking to Indian hospitals for luxury care at a more affordable cost, while the rural and urban poor have limited or no access to even basic primary care,” he commented. Dr. Shroff’s Charity Eye Hospital, founded in 1914, addresses this need with a community outreach – hub and spoke approach. The Delhi-based hospital is the tertiary institution and center of excellence, supported by 4 secondary hospitals and 20 visions centers. The Eye Hospital focus is providing quality ophthalmologic care to the almost two thirds of the population that require subsidized or free eye care.
Dr. Mathur attended a dinner hosted by the Madison Ophthalmologic Society, and also met with the staff of Combat Blindness International- an organization that partners with the University of Wisconsin Department of Ophthalmology and Vision Sciences to provide free eye care clinics here in Madison to an underserved clientele.
Dr. Mathur and his colleagues at Shroff’s Eye Hospital welcome our senior ophthalmology residents each year for an educational exchange that began in2008 and includes a cataract surgery rotation.
UW Eye Research Team Discovers Novel Gene Mutations that Cause Glaucoma
A research team of the UW Department of Ophthalmology and Visual Sciences has discovered novel mutations in a gene that are responsible for an important subset of childhood blindness called primary congenital glaucoma (PCG). Read the full article at PubMed.
The study, “Angiopoietin receptor TEK mutations underlie primary congenital glaucoma with variable expressivity,” was published in The Journal of Clinical Investigation on June 6, 2016. Dr. Terri Young, chair of the Department of Ophthalmology and Visual Sciences, is the senior author of the study performed at the UW School of Medicine and Public Health, and Stuart Tompson, PhD, a lead author of the study, is a UW associate scientist and a member of Dr. Young’s research team.
“In collaboration with an international team of geneticists, our results show that the TEK gene plays an essential role in eye health, and individuals carrying a mutation in this gene are at a much higher risk of developing newborn or later onset forms of glaucoma,” said Dr. Young.
Glaucoma is a condition that can cause vision loss when abnormally high pressure within the eye leads to optic nerve damage. PCG is a devastating inherited form of glaucoma that can present at birth through early childhood. Of note, the World Health Organization has reported that approximately 18 percent of children in institutions for the blind have early-onset glaucoma. Just as in adults, treatment options for PCG are supportive rather than curative. Many individuals undergo multiple eye surgeries, and are destined to a lifetime of applying eye medications in an attempt to decrease the intraocular pressure to normal levels.
The disease is poorly understood. Mutations in only a few genes have been linked to the disease, and account for only a minor proportion of cases. Mutations in the CYP1B1 gene are the most common cause of PCG in families with a high degree of marriage between relatives. However, it is a much less common cause in ethnically diverse populations. The researchers knew that a different mechanism must underlie the majority of these other cases, and set out to discover how that mechanism structurally alters the way the eye removes excess internal fluid.
The key risk factor for glaucoma is high intraocular pressure, which is thought to result from defects in how the aqueous humor, a renewed fluid within the eye, flows out. The Wisconsin researchers found that a key cell membrane receptor protein (known as TEK) is necessary for proper development of a drainage channel called Schlemm’s canal. If the receptor function is greatly reduced or absent due to a genetic mutation, the tubular canal is poorly formed or even absent, resulting in back-up of fluid and elevated eye pressure, which over time causes optic nerve head damage and subsequent visual field loss. Working with human patients, the UW team recruited families with at least one child with PCG, and identified 10 families that had mutations in the TEK gene. One family also had a parent with a diagnosis of childhood glaucoma, and another family contained several individuals with later-onset forms of the disease. All of the mutations identified in these families resulted in disturbance of the cellular signaling pathway necessary for Schlemm’s canal development.
“This is an important step in learning more about the biology of general glaucoma as well – a devastating eye disease that impacts more than 60 million people worldwide,” said Dr. Young. “Our discovery offers further insight into how eyes normally form a drainage system to avoid fluid build-up, and could aid in the development of new therapeutic strategies for glaucoma.” The clue to this connection came from teaming up with a Northwestern University research laboratory that studies mouse genetic models. “The collaboration with the Chicago team was critical,” said Dr. Tompson. “They engineered mice that contained mutations similar to those we had identified in our human patients. These mice displayed the hallmark signs of glaucoma and permitted the identification of defects in Schlemm’s canal underlying the disease in these cases. We can now perform prenatal genetic testing to determine who might be at risk and in need of earlier treatment before optic nerve damage can occur.”
The discovery was presented at an international vision research conference, the Association for Research in Vision and Ophthalmology, May 2016 in Seattle.
Macular Degeneration Insight Identifies Promising Drugs to Prevent Vision Loss
by David Tenenbaum, UW – Madison University Communications (July 18, 2016)
In a study published in the Proceedings of the National Academy of Sciences, a University of Wisconsin-Madison research team pinpoints how immune abnormalities beneath the retina result in macular degeneration, a common condition that often causes blindness.
Aparna Lakkaraju, an assistant professor of ophthalmology and visual sciences in the UW School of Medicine and Public Health, focused on two protective mechanisms that are compromised during the gradual onset of macular degeneration, which degrades and can destroy the central vision needed to read and recognize faces.
In tests in a mouse model of macular degeneration, drugs that are already on the market prevented damage to the cells that sustain the light-sensitive cells in the eyes.
“These studies raise the possibility of treatments that could slow or prevent macular degeneration,” says Lakkaraju.
Macular degeneration destroys central vision in about 2 million Americans, mainly among the elderly, and is largely untreatable.
Although macular degeneration eventually damages or kills the light-sensitive rods and cones, Lakkaraju explains that it starts with injury to the retinal pigment epithelium (RPE). The RPE, a single layer of cells beneath the rods and cones at the back of the eye, performs many functions essential for healthy vision. The damage starts with a disturbance of immune proteins called complement, which normally kill disease-causing organisms by boring holes in their cell membranes.
“The light-detecting cells in the retina are totally dependent on the RPE for survival,” says Lakkaraju, “but the RPE cells are not replaced through the lifespan. So we asked, ‘What are the innate protective mechanisms that keep the RPE healthy, and how do they go awry in macular degeneration?’”
In a study performed with colleagues Li Xuan Tan and Kimberly Toops, Lakkaraju focused on two protective mechanisms: the protein CD59, which regulates complement activity when attached to the outside of RPE cells; and lysosomes, spherical structures that plug pores created by the complement attack (a function that Lakkaraju’s team first detected in the RPE).
Together, they offer an in-depth defense, Lakkaraju says.
“CD59 prevents the final step of attack that forms the pore,” Lakkaraju says. “Once a pore forms, the cell can move a lysosome to close it.”
If the complement attack is not defeated, the opening in the RPE cell membrane allows the entry of calcium ions, which spark a long-term, low-grade inflammation that inhibits both protective mechanisms, creating a vicious cycle of destruction.
The inflammation in the RPE damages mitochondria, structures that process energy inside all cells. This could eventually lead to a decline or death of the photoreceptor cells, once they are deprived of their essential housekeepers. The result is the loss of central, high-resolution vision. Lakkaraju pursued her research in RPE cells isolated from pig eyes, and in mice that lack a protein — a deficiency that causes an inherited form of macular degeneration called Stargardt disease.
Crucially, her study identified an enzyme that is activated by excess cholesterol in the RPE, which neutralizes both protective mechanisms, and found that drugs used to treat depression neutralized that enzyme and restored the protection — and the health of RPE cells — in the mouse model.
Epidemiological studies by Ronald and Barbara Klein, also at the UW–Madison Department of Ophthalmology and Visual Sciences in the UW School of Medicine and Public Health, have linked long-term use of some of the same drugs with a decreased susceptibility to macular degeneration.
The drugs that helped restore protections in the RPE were chosen for their ability to remove excess cholesterol or inhibit aSMase, an enzyme involved in the toxic process, Lakkaraju says.
“There are several FDA-approved drugs that inhibit aSMase. We found that the antidepressant desipramine, administered to mice in their drinking water, restored CD59 on the cell surface, decreased reactive oxygen species, and prevented mitochondrial fragmentation.
“My lab is interested in the earliest stages of macular degeneration, because we cannot reverse the loss of RPE and photoreceptors,” Lakkaraju says. A patent application for the idea of preventing macular degeneration by blocking aSMase has been filed by the Wisconsin Alumni Research Foundation.
Given the likely increase in macular degeneration among an aging population, and the current lack of alternatives, “we hope a pharmaceutical company will license this process and start the necessary preclinical and clinical trials,” Lakkaraju says. “The epidemiological data are there, and now we have fairly convincing mouse data. The safety profiles of these drugs have been documented for decades. There is certainly no guarantee of success, but we need a way to prevent macular degeneration. I am realistic, but hopeful, that better knowledge of this disease process could be the key.”
The research was funded by the National Institutes of Health (grants #R01EY023299 and #P30EY016665), Research to Prevent Blindness, Retina Research Foundation and other sources.
PHACO 2016: Another Successful Year
In August, ophthalmology and veterinary ophthalmology residents from throughout the country came to the Department of Ophthalmology and Visual Science to learn cataract surgery. At what may be the longest consistently running Phacoemulsification course in the country, attendees at the Department’s Multiphasic Phaco Course learn about all aspects of Phaco in a three-year, progressive course that includes both lectures and wet lab practice. The goal of this course is to prepare ophthalmology students and residents to begin their Post-graduate Year (PGY) 4 cataract rotations with a sound basis in medical knowledge and skills to maximize their cataract training experience. The University of Iowa and Medical College ofWisconsin are partner institutions, bringing their residents each year as well as providing lecture and lab teachers. Veterinary ophthalmology residents come from UW, UC Davis and a variety of other veterinary programs from around the US. In 2015, the University of Kansas began sending their PGY 3 medical ophthalmology residents and this year also provided faculty.
“Our course is different from all the other Phaco courses because we have three different, level-appropriate sessions, covering the needs of beginning students and those at a more advanced level.” Said Andrew Thliveris, MD, PhD, Vice-Chair, Resident Education. The course gives our learners a one-on-one experience that will give them a jump start for the upcoming year’s training,” Thliveris notes.
Phaco 2016 provided cataract training to 47 residents and medical students with the assistance of 31 volunteers who serve as faculty.
Yao Liu, MD, Presents Telemedicine Project at Congressional Reception
UW School of Medicine and Public Health Department of Ophthalmology and Visual Sciences Glaucoma specialist Yao Liu, MD, recently returned from Washington, DC where she was an invited presenter at the Emerging Vision Scientists Congressional Reception at the Capitol building on September 14-15, 2016. Liu talked about her tele-ophthalmology initiative and the importance of funding vision research. Tele-ophthalmology uses specialized eye photos to detect eye disease in primary care clinics among patients with diabetes. These photos are then sent electronically and reviewed by eye specialists. The results are communicated to the patient’s primary care provider who refers patients with abnormal findings to local eye care providers. This type of diabetic eye screening provides rapid, high-quality eye care at low cost. It is currently available in the UW Specialty Clinic at Mile Bluff Medical Center in Mauston, WI where primary care patients can obtain eye screening on a walk-in basis.
Liu was one of 22 young vision scientists invited from across the country. Her project seeks to identify and address barriers to using tele-ophthalmology in rural health systems. This work is funded by the National Institutes of Health/National Eye Institute and the Wisconsin Partnership Program. Her overall goal is to develop and test an adaptable implementation program to expand this technology statewide and nationally. By developing a successful implementation program, Liu’s research will help increase access to eye care in underserved rural populations, address healthcare disparities, and prevent vision loss from diabetic eye disease.
According to the National Eye Institute, diabetic eye disease is the leading cause of blindness among working-age Americans. “In our country, nearly $2 billion in medical costs will be spent on treating people with avoidable blindness from diabetes–blindness that would have been prevented through earlier eye screening and treatment.” Liu said. “Unfortunately, only a half-percent of the annual medical cost of treating vision disorders in the U.S. is spent on vision research. Strong, sustained funding support for vision researchers is critical for helping us to develop better and more cost-effective treatments to prevent blindness in our communities.”
Liu was delighted to find strong support for vision research among Wisconsin’s legislators. “Kathleen Laird in Senator Tammy Baldwin’s office let us know that Senator Baldwin is a tireless supporter of research and, together with Congressman Mark Pocan, will soon be introducing legislation to provide further support for young researchers from the National Institutes of Health,” Liu said. “My colleagues from the Medical College of Wisconsin and I talked about our work, the challenges faced by young researchers, and the need for strong funding support for vision research. Jenna Mathis in Senator Ron Johnson’s office told us we were the most effective and engaging group of researchers in communicating our message that she’d ever met!”
This event was sponsored by a grant from Research to Prevent Blindness (RPB), a foundation that is seeking to preserve and restore vision by supporting research to develop treatments, preventives and cures for all conditions that damage and destroy sight.
50 in 2017: Oculoplastics Service Celebrates History
Oculoplastics fellowship graduates, physicians and friends came together September 30 – October 1 to celebrate major milestones in the history of the Department’s Oculoplastics Service. In 2016 an 18-year effort was culminated with the endowment of the Richard K. Dortzbach Professorship in Ophthalmic Facial Plastic Surgery. Only a handful of such endowed professorships in oculofacial surgery have been achieved nationwide. Also, 2017 marks the beginning of the 50th year of the Oculoplastics service at UW-Madison. Dr. Dortzbach returned to UW in 1968 from Birmingham, Alabama, to establish an oculoplastic service here after serving one of only three oculoplastics fellowships available nationwide.
The Oculofacial Celebration officially launched with a scientific conference beginning with visiting professor, Dr. James Katowitz, Professor of Ophthalmology and Director, Oculoplastic and Orbital Surgery at the Children’s Hospital of Philadelphia, presenting “Balancing Function and Appearance: An Oculofacial Plastic Perspective.” Dr. Katowitz is recognized nationally and internationally for his expertise in pediatric oculoplastic surgery. The morning’s scientific meeting comprised case studies and presentations from former fellows and UW faculty. That afternoon at Lemke Facial Surgery, Dr. Deb Sherman led a state-of-the-art skills transfer program on facial fillers. Later, Dr. Lemke, who in 1998 initiated the campaign to endow the Dortzbach professorship, thanked the donors including former fellowship graduates, former patients and families and others who helped endow the professorship.
Dr. Dortzbach entertained the audience, relating the development of the field of oculoplastic surgery after World War II and vignettes about his former fellows. Twenty prior UW oculoplastic fellows and friends of the Department attended the celebration. According to Dr. Mark Lucarelli, service director and the inaugural Dortzbach Professor, the remarkable participation in this celebration demonstrates the very special relationships within the White Coat Society. “Our history in ophthalmic plastic surgery has been truly extraordinary and we look forward to an equally bright future,” he said. “The resources available with the Dortzbach Professorship will help ensure that future.” “Dortz” thanked his friend and colleagues for honoring him, “It was perfect in every way, and I shall cherish the memories forever.” The evening ended on a lively note with Dr. Burkat leading a memorable Wisconsin version of Family Feud.