Article

RETINA CONVERSATIONS: A Conversation With Evangelos S. Gragoudas, MD

Ocular cancer, angiogenesis, PDT, and more.

Related

A native of Greece, where he went to medical school in Athens, Evangelos S. Gragoudas, MD, initially came to the United States for a residency in ophthalmology. After internship he was a pre-resident fellow at Joslin Diabetes Center in Boston, Massachusetts, and then a resident in ophthalmology at Boston University. He then completed a retina fellowship under Dr. Charles Schepens at Massachusetts Eye and Ear Infirmary. Dr. Gragoudas joined the full-time faculty at Mass Eye and Ear in 1975 and has served as Director of the Retina Service since 1985.

Although many researchers are known for a single achievement, Dr. Gragoudas’ career is distinguished by pioneering efforts in 3 major areas: treating choroidal melanoma with proton beam irradiation; developing, with colleague Joan Miller, MD, photodynamic therapy (PDT) for AMD; and developing anti-angiogenic therapies with Drs. Tony Adamis and Joan Miller. Dr. Gragoudas shared with 6 other researchers the prestigious Champalimaud Award in 2014. One of his trainees and member of his retina staff, Demetrios Vavvas, MD, PhD, is currently researching the potential of high-dose statins in the treatment of dry AMD.

In addition to his breakthrough accomplishments in retina research, Dr. Gragoudas has published more than 250 articles in peer-reviewed journals and written or authored more than 100 chapters, reviews, and books. Retinal Physician was able to catch up to this busy doctor for a conversation in which he recounts the major milestones in his career.

Evangelos S. Gragoudas, MD
IMAGE COURTESY OF DR. GRAGOUDAS

Q. How did you become interested in a career in ophthalmology, and specifically retina?

A. It’s an interesting story. When I was in medical school in Greece, we had courses in all subspecialties. There was no textbook in ophthalmology so I published my notes from the lectures of the professor and from some English ophthalmology textbooks and distributed them to my fellow classmates. Through that experience, I became very interested in ophthalmology.

Q. Did your European training in medical school differ from your early experiences as a resident in the United States?

A. Yes. In Greece we had many lectures with very little patient contact. When I came to the United States, training was much more hands-on with patients. I also had a great mentor in my residency at Boston University, Dr. Ephraim Friedman, a retina specialist who inspired my interest in doing research.

Q. How did you get involved in angiogenesis research?

A. Tony Adamis, a cornea fellow, was working at Folkman’s lab and wanted to study anti-VEGF therapy for choroidal neovascularization (CVN). We worked together with Dr. Joan Miller on a monkey model researching angiogenesis, and with the help of Dr. Napoleone Ferrara from Genentech we used Dr. Ferrara’s anti-VEGF agent (ranibizumab; Lucentis) to treat experimental CNV. We used a laser to create new blood vessels in both eyes of a monkey. We would treat one eye with the anti-VEGF ranibizumab and use saline in the other eye. The eye with ranibizumab did not show new blood vessel growth. In the eye with saline injection, CNV developed. When we treated the eye that developed CNV with ranibizumab, the new vessels regressed. It was a spectacularly successful experiment.

Q. You and Dr. Miller did the preclinical work on PDT (Visudyne). That seems like a very sophisticated concept at that early stage of learning how to treat retinal disease, using a combination approach with medication and laser activation. How did you come up with that?

A. Actually, PDT had been used in dermatology, and it was not a new concept. It had been tried in animal models with different dyes in ophthalmology without success. Dr. Miller and myself decided to try this new dye (Visudyne) in the monkey model of CNV and we succeeded in closing the new vessels without damaging the normal monkey retinal vessels. Although PDT has been surpassed by anti-VEGF treatments of CNV, it is still used effectively in central serous retinopathy, polypoidal AMD, choroidal hemangiomas, and some choroidal metastatic tumors.

Q. You have made an international reputation as an expert on ocular tumors and an innovator of proton beam therapy as a treatment. Currently, you are also an advisor to Aura Biosciences, which is conducting a clinical trial that also employs a 2-step laser-activated therapy.

A. I’m a scientific adviser to Aura, which is pursuing a treatment that destroys only the tumor cells without damaging the normal tissues. There are some promising early results, and this approach could be successful in killing tumor cells without the radiation complications.

Q. You are also involved in research using high-dose statins as a potential therapy for retinal disease. What effects can the statins have that combat the disease?

A. This is an idea of Dr. Vavvas, who is a member of our retina service. He tried high-dose statins in some patients with high-risk drusen and showed some effect. Then we did a research collaboration between Harvard and The University of Crete. This early-stage trial showed high-dose statins (80 mg) could be effective in reducing the number of drusen in dry AMD. Some improvement in visual acuity was also noted with no disease progression. Dr. Vavvas has started a company called Drusolv Therapeutics that is pursuing this area of research.

Q. Given your great accomplishments as a researcher, how important is it to you to continue to see patients?

A. It’s very important. I do continue to see patients 2 mornings a week, most of them with intraocular tumors. I also continue teaching residents and fellows, which I enjoy very much.

Q. What outside interests do you have that you pursue in your limited free time?

A. I like music, mainly classical and opera. Also, movies, theatre, and books. RP