Article Date: 1/1/2009

"Women in Retina" Group Brings Colleagues Together
SUBSPECIALTY NEWS

"Women in Retina" Group Brings Colleagues Together

They Mentor, Communicate, and Inspire.

BY RENÉ LUTHE, SENIOR ASSOCIATE EDITOR

■ There are at least 2 reasons for a group called Women in Retina (WinR) to exist, according to cofounder Nancy Holekamp, MD, associate professor of clinical ophthalmology and visual sciences at the Washington University School of Medicine, St. Louis.

One is to provide leadership development for female physicians within a predominantly male profession. The other is to remind members, in the words of a Zen Buddhist monk who recently addressed the group, of "the humanity physicians have when they take care of patients." Small gatherings at large retina meetings that allow for less formal interaction and dialogue between WinR members help to fulfill both.

The pharmaceutical company Genentech can be credited with getting Women in Retina out of the starting blocks, says Dr. Holekamp. "There was talk from numerous women retina specialists about this for a couple of years," she explains. "It was actually the women professionals at Genentech who said, ‘You really ought to do this.’" And it happened in March 2007 with a founder's board meeting in Chicago. In addition to Dr. Holekamp, the other founding physicians are Julia Haller, MD, Jennifer Lim, MD, Alice Lyon, MD, and Pauline Merrill, MD.

While the Women in Retina mission statement crafted at that time is "to be of value to women in retina by offering networking and mentoring activities not already provided by other organizations in ophthalmology," Dr. Holekamp can offer a less formal rationale.

Left to right: Alice Lyon, MD, Nancy Holekamp, MD; Puanani Burgess, guest speaker at WinR meeting; Julia Haller, MD; and WinR administrator Cordie Miller.

"Only 11% of retina specialists are women. That means there are about 2000 retinal specialists and only 220 are women. If you go to very large meetings like the Academy or the American Society of Retinal Specialists, women won't come in contact with each other often enough to have networking or mentoring opportunities," explains Dr. Holekamp. "One of our purposes is to make very large meetings smaller — so we can bring women together. Some of the issues that women face professionally are different than the issues men face professionally. In addition, it can be nicer to have a small forum for discussion of interesting cases, common practice issues, or shared life choices."

To provide those smaller forums, WinR conducts functions (sponsored by industry) at the major retinal meetings. Dr. Holekamp says Women in Retina offers 2 events at the annual American Society of Retinal Specialists meeting and 1 event at both the American Academy of Ophthalmology and the Association for Research in Vision and Ophthalmology meetings. And the group is fine-tuning its plans for the future as it learns what topics most interest its members.

"For 2009, we've heard a request from our constituents that they would like a panel discussion of prominent women in retina, so that they can discuss how they ‘did it’ — how they were able to do research, publish, have a busy practice, raise a family, and volunteer in their communities," says Dr. Holekamp. "Hopefully, this panel format will lead to discussion between women who have found the right balance and the audience members who have a range of choices to make."

Holding its events at the major meetings is part of a strategy to make Women in Retina user-friendly for its members. "If you are a retinal specialist, there are a lot of meetings," explains Dr. Holekamp. "If you have kids and a practice, you don't want to head to another meeting that's called Women in Retina. We always want to have functions at meetings women are going to anyway."

Anyone who is a member of ASRS is automatically a member of WinR and so eligible to attend these events; the group is open to other women by invitation. For more information, e-mail Dr. Holekamp at nholekamp@gmail.com.

Considering Long-term Anti-VEGF Effects

Animal Study Encourages Vigilance in Humans.

RESEARCH FROM SCHEPENS EYE RESEARCH INSTITUTE

■ Scientists at Schepens Eye Research Institute have found that reducing the levels of VEGF in adult mice causes the death of photoreceptors and Muller glia — cells of the retina that are essential to visual function.

This finding was recently published in PLoS ONE, an interactive, peer-reviewed online journal sponsored by the Public Library of Science. The research, if confirmed in humans, could hold implications for the long-term use of anti-VEGF drugs, which act to eliminate abnormal and damaging blood vessel growth and leakage in the retina by neutralizing VEGF.

"The take-home message of this study is that physicians should be vigilant in monitoring patients undergoing anti-VEGF treatments for any possible signs of these side effects," says Principal Investigator Patricia D'Amore, PhD, senior scientist at Schepens Eye Research Institute. Anti-VEGF drugs "are very good at reducing the edema (fluids) and eliminating the abnormal blood vessels that characterize wet macular degeneration, but our results suggest that there could be unanticipated side effects."

Scientists have long known that VEGF is essential for normal development of the vascular system and for wound healing. Unfortunately, VEGF also stimulates the growth of abnormal blood vessels that leak and damage retinal tissue. However, Schepens researchers say that a growing body of evidence also indicates that, beyond its impact on blood vessel growth, VEGF may play other vital roles in the adult body and eye, so that eliminating the growth factor might lead to unexpected consequences.

Given the popularity and promise of the new anti-VEGF drugs for the treatment of macular degeneration, Dr. D'Amore and her team believed that investigating the broader role of this growth factor in the normal adult retina was critical. She and her laboratory mimicked the action of the anti-VEGF drugs by introducing into adult mice a soluble VEGF receptor, known as sFlt1, which binds and neutralizes the VEGF in much the same way that ranibizumab does in the eye.

After 2 weeks, the team found no effect on blood vessels of the inner retina but did find a significant increase in the number of dying cells of the inner and outer nuclear layers, which include amacrine cells that participate in transmitting the visual signal; Muller cells that also participate in the visual signal and support the photoreceptors; and photoreceptors, which are responsible for color and night vision. The team then used electroretinograms to measure visual function and found a significant loss in visual function. Consistent with these observations, they discovered that both photoreceptors and Muller cells express VEGFR2, the major VEGF signaling receptor, and they found that neighboring Muller cells express VEGF.

Parallel studies in tissue culture demonstrated that suppressing VEGF in Muller cells led to Muller cell death, indicating an autocrine role for VEGF in Muller cells (i.e., Muller cells both make VEGF and use it for survival). Further, they used cultures of freshly isolated photoreceptors to show that VEGF can act as a protectant for these cells.

"Insight into the complex role of VEGF in the eye and in other parts of the body indicates that increased care should be taken in the long-term use of these drugs and that this new information should be considered in the design of future clinical studies to ensure that these possible side effects are taken into account," says Dr. D'Amore.

"Mice eyes differ from human eyes in many ways, so we cannot directly extrapolate these results to humans, but this study is an important headsup that clinical application of anti-VEGF therapy in the eye needs to proceed with caution," she adds.

CORRECTION
In the November/December issue of Retinal Physician, an article in the news section detailed clinical findings for the various patient cohorts in the phase 3b HORIZON study of ranibizumab. The third-year results for both the "cross-over" group and the "untreated" group were reported incorrectly.
The correct findings are as follows: Patients in the "crossover" group averaged a 2.4 letter loss of vision in the third year despite receiving ranibizumab for 1 year. Patients who went totally untreated with ranibizumab for all 3 years averaged a 3.1 letter loss of vision in the third year. All other data pertaining to the trial were reported correctly in the article. Retinal Physician regrets the error.

IN BRIEF
Implantable telescope for end-stage AMD. VisionCare Ophthalmic Technologies Inc, a developer of advanced visual prosthetic devices for individuals with AMD, said 2-year results from the phase 2/3 trial of its implantable miniature telescope showed substantial visual acuity improvement in end-stage AMD patients. The results were published recently in the American Journal of Ophthalmology.
The study device, a first-of-kind implantable telescope, has already received CE Mark approval in Europe and is currently under regulatory review by the FDA.
The journal article details the safety profile of the device and found rates of cornea endothelial cell loss, while higher than conventional smallincision anterior-segment eye surgery, were consistent with anterior-segment procedures employing the more similar incision sizes required for telescope implantation.
"The published data show improved visual acuity in end-stage AMD patients that was maintained over 2 years – a 3-line improvement that we have previously shown makes a real impact on our patients' independence and quality of life," said Henry L. Hudson, MD, lead author for the IMT002 study and retina specialist in Tucson, AZ.
"The data presented confirm the effectiveness of the AMD telescope prosthesis and the long-term safety profile of the device," said R. Doyle Stulting, MD, PhD, professor of ophthalmology at Emory University in Atlanta and study coauthor. "Key indicators of corneal health and diagnostic verification of device placement substantiate earlier findings that risks of surgery are outweighed by the benefits the improved vision brings to these patients' lives."
Reports of inflammation with Avastin. Genentech issued a "Dear Healthcare Provider" letter in December to inform physicians of 36 reported cases of intraocular inflammatory reactions following off-label intravitreal injection with Avastin in Canada. The letter was posted on the company web site at www.gene.com and mailed to retina specialists.
The cause of the cases in Canada is as yet unknown. Genentech said there is no evidence to suggest there is an increased risk of serious eye inflammation with Lucentis. Genentech also noted that Avastin is FDA-approved only for oncology indications and is formulated for intravenous use for those indications. The Avastin lot linked to the Canadian inflammation incidents was not distributed in the United States.
OPKO wet AMD trial. OPKO Health has completed enrollment in the company's phase 3 clinical trial of bevasiranib for the treatment of wet AMD. The multinational study has enrolled more than 330 patients and is designed to assess the efficacy and safety of bevasiranib administered every 8 or 12 weeks in preventing vision loss due to wet AMD.
"This first-ever phase 3 trial of an agent based on RNAi technology is a milestone in the field of RNAi," said Phillip Frost, MD, chairman and CEO of OPKO Health.
Retina Regeneration trial data. Ellex has announced positive 6-month data for its laser-based Retina Regeneration Therapy for macular edema secondary to diabetic retinopathy (DR).
In a clinical study conducted at St. Thomas Hospital in London, 17 patients (28 eyes) with newly diagnosed DR completed 6-month followup after treatment with the Ellex 2RT Q-switched green YAG laser producing precise, 3-nanosecond pulses of 532 nm light energy. At 6 months, 46% of the patients had a decrease in central macular thickness of more than 5% from baseline and 43% of eye had an improvement of 2 or more lines of LogMar visual acuity.
Geographic atrophy trial begins. Alimera Sciences Inc. said that enrollment has begun for a pilot study to assess the safety and efficacy of the Iluvien insert in patients with bilateral geographic atrophy (GA) secondary to AMD. The pilot study will compare 2 doses of Iluvien (0.23 and 0.45 micrograms per day) to sham injection. The change from baseline in size of geographic atrophy will be assessed over time.
Iluvien, a tiny, intravitreal insert, is currently being studied in the FAME phase 3 clinical trial as a way to deliver a very low dose of fluocinolone acetonide to the retina for up to 3 years as a treatment for diabetic macular edema. The Iluvien insert is placed into the vitreous in a minimally invasive outpatient procedure.
Dr. Ambati wins research grant. Jayakrishna Ambati, MD, of the University of Kentucky, has received the prestigious 2008 Doris Duke Distinguished Clinical Scientist Award. The award provides $1.5 million in research funding over the next 5 years. Dr. Ambati is widely known for his controversial views on the use of small interfering RNA molecules (siRNA) to treat degenerative retinal disease. He believes these investigational drugs can have potentially dangerous systemic side effects.
Dr. Ambati is one of only 6 physician-scientists in the nation to receive the 2008 award, given every other year. He is the first ophthalmologist to receive this honor from the Doris Duke Charitable Foundation. RP


Retinal Physician, Issue: January 2009