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RETINA CONVERSATIONS: A Conversation With William R. Freeman, MD

A rewarding career in an academic setting.

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Any young ophthalmologist seeking career guidance would be well served to look at the achievements in academia of William R. (Bill) Freeman, MD, vice chairman of the Department of Ophthalmology and director of the Jacobs Retina Center at the Shiley Eye Institute of the University of California San Diego (UCSD).

Dr. Freeman is an unabashed advocate of the advantages of the academic setting, which affords him the opportunity to see 80 or 90 patients a week, have time set aside for his highly productive research initiatives, serve as an effective administrator/mentor, and be able to draw upon the considerable multi-discipline brainpower that an academic institution such as UCSD offers.

Dr. Freeman, a New Yorker who moved to California for his fellowships and stayed, served notice early in his career that he was destined to make important contributions to the retina subspecialty. He arrived in California just as the AIDS epidemic was peaking and pioneered innovative techniques to combat new forms of retinal detachment that were first seen with the AIDS onslaught. He was funded for more than 25 consecutive years by the National Eye Institute, holding RO-1 grants continuously.

In more recent years, he has developed his interest in patient-friendly drug-delivery concepts, working with Allergan to advance a sustained-release, biodegradable brimonidine implant for geographic atrophy into a current phase 3 clinical trial. Dr. Freeman has also led the way in using 4 mg high-dose Eylea (Regeneron) for difficult-to-treat wet AMD patients, a concept that Regeneron will itself explore in a study planned to begin this year.

Despite a busy schedule, Dr. Freeman has also found the time to help found 2 retina-related start-ups. Retinal Physician recently caught up with Dr. Freeman for a conversation that is both compelling and revealing of his concerns for the future of the medical profession.

William R. Freeman, MD
PHOTO COURTESY OF DR. FREEMAN

Q. Why did you choose ophthalmology, and specifically retina, for your medical career?

A. For me, I thought it would be more satisfying to directly treat people and make them better, rather than making small medicine interventions and then monitoring patients for improvement, which is what I saw in my general medicine rotations. I also liked the idea that there was an important surgical component to retinal practice and a requirement to know a lot of internal medicine.

Q. Who were your most influential mentors along the way?

A. My earliest area of interest was uveitis, so I did my residency at Lenox Hill Hospital in New York City under Robert S. Coles, MD, who was considered a leading uveitis expert. I then completed 2 fellowships in California, at University of California San Francisco (UCSF) and University of Southern California (USC). The first was in uveitis and second, a 2-year fellowship in surgical retina at USC/Doheny Eye Institute. At UCSF, I was a proctor fellow under G. Richard O’Connor, MD, who was probably the most influential American ophthalmologist of his generation. He had a great mind. He picked up physical clues, even before he examined the patient, and he studied patients’ histories. He could often make the correct diagnosis based on those factors alone. I also worked with Devron Char, MD, studying ocular tumors and the immunology of uveitis. In his laboratory, we analyzed aqueous cells from patients with uveitis.

One of the greatest influences on my career was my time at Los Angeles General Hospital. This was like being in the front line on a retinal battlefield, with low-income patients, an underserved community, and equipment that wouldn’t work unless you could fix it yourself. This was valuable experience for a young physician. It taught me to understand the function of our surgical equipment and how to improvise. If patients had poorly controlled medical problems, it was often me who would change drug regimens to prepare a patient for surgery.

Q. You became very involved in AIDS research early in your career.

A. It was the height of the AIDS epidemic, and there was a great urgency to attempt to combat the dreaded and mysterious disease that was taking so many lives. It was a tremendous challenge for ophthalmology, because we were seeing things that we had never seen before, different types of retinal infections and rare retinal detachments. It was all new. I wrote the first paper on how to repair complicated retinal detachments due to infectious retinitis using techniques that at the time were controversial (using silicone oil primarily) but proved to be correct. I had NIH funding for 25 years researching cytomegalovirus retinitis, as well as developing new forms of ocular drug delivery. Overall, I would say that the early part of my career focused primarily on HIV disease.

Q. How have your research interests evolved over the years?

A. I like to try new things that can make a positive difference in patients’ lives, developing concepts that are better than what’s out there. I do think that better, longer-lasting drug formulas for drug delivery is a priority for both physicians and patients, especially for retinal disease. I have worked in the laboratory to develop nanoporous silicon and prior to that liposomes to extend the drug activity time after intravitreal injections. Working with Allergan, we have advanced the brimonidine sustained-release implant for geographic atrophy into phase 3. It’s promising for a still unmet medical need. Allergan is calling the shots on that one.

And we’ve been successful using 4 mg high-dose Eylea for difficult-to-treat wet AMD patients. It’s part of our step-by-step treatment regimen that has produced positive results. We’ve written 3 papers on the concept that are available on PubMed.

I’m excited about our own startup company, Spinnaker Biosciences, that was founded by myself and my colleague at UCSD, Michael Sailor, PhD, a professor of chemistry and biochemistry. The concept involves drug delivery by way of microparticles with nanopores into which drug can be loaded. The pores are on the molecular size dimension and packing drug in nano-sized pores allows highly controlled release of drugs from the particles into the vitreous. The particles themselves dissolve. If we have success, we can reduce the treatment burden for retinal disease by providing a longer-acting sustained-release delivery system.

Another startup in which I am a cofounder is Nanovision Biosciences, which is developing an advanced retinal prosthesis with 1,000 to 3,000 electrodes, which will be implanted subretinally and provide a much clearer image than the 60-electrode retinal prosthesis that is FDA approved. A great thing about this venture is that we have a multidisciplinary team, primarily from UCSD and our great school of engineering, just a tremendous amount of brainpower that we were able to draw on. We expect to begin a clinical trial in about a year.

Q. You are a strong advocate for a career in academia. Why so?

A. First, you get to be involved in teaching high-level people and you are expected to make contributions that advance the field. I am given the time to do important research and collaborate with top experts within the institution. It is hard to do serious research in private practice. Certainly, one can present papers and clinical trial results based on drug company results and data. However, this is more like being a spokesperson for a pharmaceutical or device company. These companies have large research and public relations teams, and although many of these companies are innovative, in our current system, physicians often are asked to speak for them.

Q. You have some real concerns about the future of the medical profession.

A. Right, and I’m not happy about it. Corporations are taking over the practice of medicine. Many of the clinical presentations at meetings are organized and funded by drug or device companies. Profit-oriented practice guidelines will be coming to the physician via insurance companies and soon via EMR. Electronic medical record systems are now ranking physicians based on government-mandated questionnaires that are only tangentially correlated with practicing good medicine. Overall, physicians are losing independence because these integrated health systems are designed to manage physicians and limit their treatment choices for patients.

Q. You have a large family and a couple of interesting hobbies. Could you tell us something about that side of your life?

A. My wife, Dr. Laura Gomez, is also an ophthalmologist who treats the anterior segment, specifically dry eye. Many AMD patients also have a dry eye disease that makes their impaired vision worse; so, we get to collaborate at times. We have 4 children and we spend a lot of time with them. I have always encouraged all of my children to have a profession. Two became attorneys, we have one about to go to college, and our youngest is a sophomore in high school. My wife and I make it a habit to almost always be home for dinner. It is important to have a reliable family life.

My hobbies are archery and kite surfing, which I have tried to teach my children. Most weekends, you’ll find me on the water. That’s my getaway. The challenge there is jumping longer and higher, surfing the waves while handling the kite. One feels united with nature. Also, often many good ideas come to me while I am spending time doing my hobbies. Being able to share activities with my family is also a rewarding and uniting experience. RP