How and why did you become an ophthalmologist?
In the first two years of medical school, we were taught by internists and medical subspecialists who considered themselves more intellectual than surgeons. As such, I didn’t really give surgical subspecialties much thought. However, one of my first clerkships was in orthopedic surgery with a superb female resident, Dr. Colleen Kennedy, and I loved it. I thought about choosing orthopedics as a specialty, but at that time, I was expecting our first child, and the ortho residency schedule was daunting. My intern in medicine suggested ophthalmology, as it combined medicine and surgery, cared for patients of all ages, and, like orthopedics, was a specialty that sought to improve a patient’s function and quality of life. I spent a half day in an ophthalmologist’s office (Dr. Claudia Richter) and then did six months of lens research with Dr. Judy Jedziniak during the required year off from medical school after having our baby. I thought ophthalmology was a great choice and still do.
Were there specific mentors that influenced your career?
I have been blessed by having wonderful mentors for different aspects of my professional life. Drs. Evan Gragoudas and Don D’Amico were great teachers of medical and surgical retina, respectively, and continued to serve as clinical mentors throughout my career. Dr. Judah Folkman, the father of angiogenesis, was an important science mentor, as was Dr. Patrica D’Amore who was in Dr. Folkman’s research group at the time, and later came to Mass Eye and Ear. Dr. Ephraim Friedman was also a scientific mentor but was especially helpful to me as a leadership mentor; he was the one who encouraged me to apply to be Department Chair at Mass Eye and Ear and Harvard Medical School. I was fortunate to have fantastic and innovative collaborators, including Drs. Tony Adamis and David Shima. Now, I have a wonderful and talented group of lead investigators in our AMD research group, who were once mentees and now are colleagues, including Drs. Demetrios Vavvas, Deeba Husain, John B. Miller, Ivana Kim, David Wu, and Inês Laíns. I look forward to continuing our efforts to solve unmet needs in AMD and the retina field.
What are some of the main obstacles or challenges you have faced throughout your career?
There are both challenges and opportunities as a clinician scientist. Scientifically, one is competing with full-time scientists for grant funding and productivity, while also balancing a clinical and surgical practice. Clinically, you want to remain busy in order to continue learning new surgical techniques and to become and remain a stellar surgeon. On the upside though, having a foot in both worlds allows you to learn from your patients daily, understanding the current unmet needs in ophthalmology. As a clinician scientist, you can problem solve in a productive way, understanding and pursuing the science, while maintaining a clear understanding of what scientific innovations would be practical and meaningful for patients.
I really enjoyed my career as a surgical retina clinician and translational research investigator and never set out to be Chair of a department. However, in the early 2000s, our department, and Mass Eye and Ear as an institution, were struggling with leadership challenges. My mentor, Dr. Ephraim Friedman, told me that while I had been successful with my own career as a clinician scientist, it was now my time to give back to the institution, and build an environment to support young people to succeed as I had done. That was a compelling argument, and I threw my hat in the ring to be Chair and was ultimately selected.
In the early days, I was terrified by the thought that if I messed up as the first woman Chair of the Harvard Medical School Department of Ophthalmology, I would set things back for women by a decade. I used to drive into work listening to “Les Mis” to psych myself up. Well, after serving as Chair for 22 years, I think I did a good job and I had the pleasure of working alongside great administrative partners and faculty leadership teams. Together, we tripled the size of the department, brought Schepens Eye Research Institute back into Mass Eye and Ear, fostered innovation and translational research, and built strong educational and training programs supported by a formal mentoring program. I have to say, the best part of the job is the people. However, the most challenging part of the job is also the people. I enjoyed my work as Chair and leader of the department tremendously, but now am excited to have more time to devote to research while I am still able to contribute.
Can you describe your proudest professional moments?
When I finished my training in 1991, neovascular AMD was a great unmet need and I wanted to find a better treatment. I had become interested in photodynamic therapy (PDT), doing research as a fellow, and as a junior faculty member carried these experiments even further. Evan Gragoudas worked with me on PDT, along with wonderful research fellows, including Michal Kramer and Deeba Husain. PDT using Benzoporphyrin derivative (or Verteporfin) was in clinical trial for metastatic skin cancer, which meant that if I could demonstrate effectiveness in models of neovascular AMD, there would be an easier path to clinical trial. This meant first going to Coherent, an ophthalmic laser company in California to ask them to build a laser that could deliver the lower power laser light needed through a slit lamp to treat macular lesions with PDT.
George Marcellino, David Dewey, and Tom Brunner at Coherent were so helpful, and with their prototype laser we proceeded with the experiments. One of the early challenges was that the parameters being used for tumors necessitated very long laser application times, which I realized were not practical when treating the macula. I decided to increase the laser irradiance even though this flew in the face of expert dogma; but eureka – it worked! Our successful experiments led to successful clinical trials, which led to regulatory approval for the first treatment for AMD. It was very exciting to be involved in the proverbial bench to bedside – going from laboratory experiments to patients, and then to clinical trials and an approved therapy that was used worldwide.
During the time that we were working on PDT, Drs. Tony Adamis, Pat D’Amore and I were investigating the drivers of ocular angiogenesis. This work demonstrated the key role of VEGF, and led to anti-VEGF therapies that largely supplanted PDT, and are now used to treat millions of patients annually around the world. I am honored to be a part of these two very exciting stories and breakthroughs in ophthalmology.
What are the major changes in the retina space you have witnessed through your career?
Ophthalmology is a very innovative specialty and will hopefully remain so. Retina has changed from a strictly surgical specialty to one that is heavily pharmaceutical, with the advent of anti-VEGF therapies and other approaches. Ophthalmology was the first area of medicine to have an approved gene therapy for a genetic disease – Leber congenital amaurosis (LCA) RPE 65. Ophthalmology, particularly retina, has seen great advances in ophthalmic imaging that continue to change the way we understand and manage retinal diseases. There has also been surgical innovation in ophthalmology, including lamellar surgery, 3D surgical techniques, small gauge vitrectomy, use of staining during surgery, and perfluorocarbon liquids.
In the US, there has been a disruption in the business model of ophthalmology with the introduction of private equity. This has raised concerns related to the provision of care with poorer reimbursement, including neuro-ophthalmology and pediatric ophthalmology.
As with many areas of our lives, AI will undoubtedly change ophthalmology. Certainly, deep learning algorithms may be able to identify biomarkers for progression in a variety of conditions. AI may also accelerate drug discovery and will likely provide diagnostic and decision-making support in the future.
What are your main interests within ophthalmology right now, and what excites you most about your current work?
I am now working as a full-time faculty member focused primarily on research with some limited patient care. I am excited to have more time to think and to read; and I am honored to be working with a great group of clinician scientists working on AMD and other retinal conditions: Demetrios Vavvas, Deeba Husain, John B. Miller, Ivana Kim, David Wu, and Inês Laíns.
Our group believes that early and intermediate AMD are comprised of multiple disease subtypes rather than a single disease. Each subtype is potentially driven by different mediators, ultimately culminating in the same advanced stages of the disease. We are working to better characterize these subtypes through a combination of demographics, functional testing – including quantitative contrast sensitivity and dark adaptation – metabolomics, genomics, proteomics, and imaging including OCT-angiography and also developing deep learning algorithms to characterize imaging biomarkers. With our collaborators, we are using novel statistical approaches to combine the large datasets that are generated.
Using these approaches we have been able to develop biomarkers to predict disease progression, and we anticipate that we will also uncover novel targets for treatment. Along the way, we are pursuing targets of interest already identified, including intensive lipophilic statin treatment in intermediate AMD as well as neuroprotection.
Looking forward, are there any specific developments you would still like to see?
In AMD, we would like to be able to treat patients early so that they never lose vision. More broadly, we would aspire that every child born today will see throughout their lifetime.
What advice would you give to ophthalmologists starting out on their career journeys?
Ophthalmology remains a great specialty. We have the privilege of making a huge impact in our patient’s lives with our medical and surgical interventions, directly improving their visual function and quality of life. Where we don’t have effective treatments, we can help our patients by educating them about their disease, identifying other resources, and engaging them in research, so that they are able to recognize that there is hope.
I would remind young ophthalmologists to listen to their patients. Remember that your patients come to you in a vulnerable state – fearful of going blind, and dependent on your professional care and support. It is a great privilege to care for our patients.
