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RETINA CONVERSATIONS: A Conversation With Scott W. Cousins, MD

Committed to advancing medical retina.

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Halfway through his studies at Case Western Reserve School of Medicine, Scott W. Cousins, MD, remembers “getting bored” with the focus on routine clinical care — so he decided to take time off to pursue laboratory research. He found his way to Stanford University and the lab of James Rosenbaum, MD, a young ophthalmologist who was conducting research in mechanisms of inflammation, uveitis, and ocular immunology. This formative experience solidified his career choice in ophthalmology.

As he pursued his education through the completion of medical school, ophthalmology residency at Washington University in St. Louis, and a 2-year fellowship in vitreoretinal surgery at Bascom Palmer Eye Institute, Dr. Cousins began to recognize that, like other areas of medicine such as oncology, retina had the potential to evolve from an exclusively surgical subspecialty to a subspecialty with a strong medical component.

As he saw his vision for the future of medical retina become a reality, Dr. Cousins chose to give up surgery 15 years ago, with the sole focus of making the Duke Eye Center and Duke Center for Macular Diseases a leading center of innovation in medical retina. Today, he is the Robert Machemer, MD, Professor of Ophthalmology and Immunology, vice chair for research, and director of the Duke Center for Macular Diseases at Duke Eye Center. As vice chair, he oversees all basic science research as well as the Ophthalmology Clinical Research Unit, which manages the clinical research enterprise of the Duke Eye Center. Dr. Cousins also serves as the medical director of hospital-based therapies and procedures for Duke Eye Center.

At Duke, Dr. Cousins is involved in several new and promising areas of retinal research, including a potential therapeutic approach to address the problem of anti-VEGF resistance in neovascular AMD and a novel mitochondria-targeted drug, which has the potential to become the first drug to improve visual function in patients with dry AMD.

Scott W. Cousins, MD.
IMAGE COURTESY OF DR. COUSINS

Retinal Physician was able to catch up with this busy clinician–researcher for a wide-ranging conversation about his current work and how his early insights on the bright future of medical retina have come to fruition.

Q. In addition to Dr. Rosenbaum at Stanford, who were some of the other mentors who had the greatest influence on your career?

A. I’d start with Bernard Becker, MD, chair during my residency at Washington University in St. Louis. At Bascom Palmer, I worked under Edward W. D. Norton, MD, who chaired the department and headed the retina group, along with George Blankenship, MD, and Harry Flynn Jr., MD. I still talk to Dr. Flynn on a regular basis. He remains a leading authority on endophthalmitis, which is a concern for all retinal specialists.

Q. Most retina specialists will tell you that their first love is surgery and that they don’t like the fact that they are spending most of their day giving injections. Yet you gave up doing surgery many years ago.

A. That’s right, and I don’t regret it for a minute. The way I see our profession evolving is for vitreoretinal surgery to become more and more outcomes based and time based. The surgeons who achieve the best outcomes with the greatest efficiency will be in high demand, and this may even ultimately influence reimbursements. I envision the field of retina stratifying into 2 groups: surgical specialists and medical specialists.

Q. We understand that you are quite enthusiastic about novel therapeutic avenues in medical retina. Please tell us about what may be on the horizon for patients with wet AMD.

A. Our medical retina group at Duke has been conducting dual prospective investigator-investigator studies, the PERSIST and RESIST studies, for patients with wet AMD who are poor responders to anti-VEGF therapy. From the PERSIST study, we know that 25% of wet AMD patients receiving aflibercept (Eylea; Regeneron) have persistent disease in spite of anti-VEGF. With bevacizumab (Avastin; Genentech), that rate is even higher, jumping to 40%. We have also observed that the vast majority of anti-VEGF resistance is associated with the presence of CNV with arteriolarization and perivascular fibrosis.

In the RESIST study, we have been studying the clinical efficacy of adjunctive verteporfin photodynamic therapy (PDT) for anti-VEGF–resistant disease. We believe that the addition of PDT, directed at the base of large feeder arterioles, will be effective in optimizing anti-VEGF treatment, achieving disease quiescence while managing treatment burden. Optical coherence tomography angiography may also help us to identify and target those vessels. This would be a revival for PDT, which is still used with good results as a therapy for central serous retinopathy. It is possible that soon, PDT laser equipment will be reintroduced to the retina community. Currently, only a minority of retina specialists have PDT lasers available to them.

In the laboratory, our group has shown in mouse models that inflammation drives the formation of arteriolarized CNV that is resistant. So, we believe that a future therapy targeted against inflammation, given in combination with anti-VEGF, could achieve optimal outcomes for poor responders.

Q. You were also the lead investigator in a very promising early-stage clinical trial for dry AMD. In this trial, patients actually saw improved vision.

A. Yes, In the phase 1 ReCLAIM study conducted by Stealth Biotherapeutics, 40 mg of mitochondrial-targeted elamipretide, administered by subcutaneous injection daily for 24 weeks, showed encouraging results in both improved visual acuity and greatly increased low-luminance reading ability (mean of +5 lines) in a subgroup of 19 individuals with noncentral geographic atrophy (NCGA). Patient-reported outcomes on the low-luminance and the National Eye Institute Visual Function Questionnaire paralleled these results, demonstrating statistically significant improvement in daily quality-of-life measures, especially those related to low-luminance visual function. What was both exciting and remarkable was the clear potential for improved visual function, as opposed to other investigational drugs, where slowing disease progression has been the goal.

A second 21-patient subgroup of the ReCLAIM study with dry AMD and high-risk drusen but no GA diagnosis also received elamipretide under a similar protocol and also showed mean improvement in visual acuity and low-luminance reading ability at 24 weeks. Elamipretide received fast-track status from the FDA in December. Stealth has recently advanced elamipretide into a 48-week, 180-patient phase 2 study for NCGA.

We reported the ReCLAIM data at the 2019 ARVO meeting and noted that individuals with NCGA have significantly better baseline BCVA than people with central geographic atrophy, with a better potential for vision improvement.

Q. Dry AMD and geographic atrophy has been a tough nut to crack. It’s still considered a major clinical unmet need. We’ve had some therapies that looked promising but failed in late-stage clinical trials. Besides elamipretide, what other approaches appear to have potential?

A. I think we are going to need combinations to successfully treat dry AMD. Allergan has advanced its brimonidine implant into phase 3 trials, a therapeutic strategy that is based on neuroprotection. David Zacks at the University of Michigan has done a lot of work focused on preventing photoreceptor cell death (by inhibiting the FAS pathway with a peptide drug). We may see a clinical trial for that concept soon. Allegro recently reported positive top-line results for its anti-integrin therapy in patients with dry AMD. There are a number of different strategies being studied that are not overlapping, which I think will be essential in the clinic.

In a related area, I believe we are going to see advances in home-based diagnostic devices, such as the home OCT from Notal Vision, that will be more sensitive and specific in the early detection of conversion from dry to wet AMD.

I am very optimistic about the what the future holds in AMD specifically and in medical retina more broadly. We are very lucky in the retina community to have a lot of very intelligent, collegial investigators pursuing a depth and breadth of research that is impressive and has the potential to impact clinical care.

Q. You chose a career in academia. What do you see as the advantages and disadvantages of academia vs private practice?

A. If you want to do lab-based research as we do here, or translational research, you really need the resources and depth of multidisciplinary talent that only an institution such as Duke can provide. Clearly, if you want to teach you should be in academia. Another advantage is that if you have a complicated or unusual clinical case, you can easily connect to a world-class colleague for a quick consult.

But on the other side, if you want to buy a piece of equipment, say a laser, or if you want to initiate clinical trials, you have to deal with more approvals and rules and regulations of the institution, which take time. In private practice, you can sit down with the partners or the practice manager, and you can make these decisions much more quickly and efficiently.

Q. What do you like to do in the limited free time that your work allows you?

A. We have 2 daughters, so I try to balance my work time with family time. I love to cook and grill for family and friends. Aside from that, I used to be a pretty good golfer but to devote 7 hours to a golf game was just too much, so I gave that up a few years ago. RP