I love my job. Not every hour, and not every moment of it—daily frustrations can certainly abound. Nonetheless, the hassles of scheduling issues, budget cuts, and personnel squabbles are relatively minor when I consider how lucky I am to be a retina specialist in this new age of medical advances. When I first came to work at Joslin Diabetes Center, Dr Lloyd M. Aiello—a gifted clinician, generous mentor, and pioneer of laser treatment for diabetic retinopathy—recounted stories of treating diabetic eye disease in the 1950s, 60s, and 70s. He recalled waiting rooms filled with patients and their seeing-eye dogs. Every year, 50% of his patients died and 50% went blind from diabetic eye complications. In the 1950s, the 5 year life expectancy of a patient diagnosed with proliferative diabetic retinopathy was only 30%. These days, I rarely see a patient accompanied by a guide dog. A study of the visual outcomes in Joslin patients a few years ago revealed an average visual acuity of 20/20, with few cases of legal blindness. And I hope and fully expect to build relationships with my existing patients, both with and without proliferative diabetic retinopathy, over multiple decades.
It’s not just in the field of diabetes that we’ve seen tremendous advances. Over the last 15 years, I have witnessed the course of neovascular age-related macular degeneration change dramatically. Whereas patients with this condition used to rapidly and irreversibly lose vision, those who are treated in a timely and appropriate fashion with long-term intravitreous anti-vascular endothelial growth factor (anti-VEGF) therapy can now maintain excellent functional vision for years. Retinal surgery has also been revolutionized by the advent of smaller-gauge vitrectomy instruments. Our patients have benefited from sutureless techniques that allow faster operating times and more delicate tissue manipulation. Even as we’ve discovered new therapeutic modalities, we’ve also made progress in accessing previously inaccessible patient populations. Mobile screening vans and portable laser instruments have made patient triage by telemedicine and local treatment possible even for those who have historically lacked access due to geographic or socioeconomic barriers.
So how have we come so far in such a short period of time? Is it hard work? Coincidence? Luck? Our surgical advances owe much to the hard work of leaders in the field who have collaborated with engineering experts to develop newer and better instrumentation. In the fields of both surgical and medical retina treatment, we have also benefited from fortuitous discoveries. But much credit is also due to the thoughtfully designed and implemented clinical trials that have revolutionized care in this field, especially when it comes to the medical treatment of retinal pathology.
Over the last few decades, we have been extraordinarily successful at leveraging discoveries from clinical observation and from our translational science colleagues into new therapies and treatment approaches. Phase 3 studies, from the Diabetic Retinopathy Study and Early Treatment Diabetic Retinopathy Study which first proved the efficacy of laser treatment for diabetic eye disease, to more recent anti-VEGF trials that have replaced laser with anti-VEGF therapy as first-line treatment for diabetic macular edema, neovascular age-related macular degeneration, and retinal vein occlusion, have set ever increasing expectations for optimal visual outcomes in our retina patients.
I like to think I’ve learned a few lessons over my last decade as a clinical researcher. The earliest of these was the integral concept that a well-designed trial provides equipoise for investigators and study participants alike. Both should fully believe that any of the treatments being compared could have the most benefits or fewest risks for participants. It is unethical to participate in a study in which one of the treatment assignments is clearly better for a patient.
I’ve also learned to never take the outcome of a study for granted, no matter how promising the results from earlier trials. We have been surprised time and again when agents with positive results in preliminary, proof of concept studies are shown to be ineffective once they are evaluated in larger, phase 3 trials. The most recent casualty in potential new therapies has been pegpleranib, an anti-platelet derived growth factor agent, which in combination with ranibizumab was superior to ranibizumab alone for neovascular age-related macular degeneration in a phase 2b trial, but which failed to demonstrate superiority in 2 phase 3 studies reported at the end of 2016.
Given the ever-present possibility that a novel treatment might fail, it is important to design every study so that the results, whether negative or positive, add valuable knowledge to the field. In recent years, we have gained critical insights from control groups enrolled in studies of anti-VEGF for diabetic eye disease to help us better understand the natural history of diabetic retinopathy progression in the era of modern blood glucose, hypertension, and lipid control. Finally, and perhaps most importantly, I’ve learned that a successful trial is the accomplishment not solely of investigators who may have helped design and enroll the protocol, but of the entire study team, including study coordinators, ophthalmic technicians, participants, and coordinating center staff.
I love being a retina specialist because this career has given me effective tools to make people’s lives better on a daily basis. My work in the clinic lets me change the lives of individuals one at a time. My work as a clinical researcher has the potential to positively impact the lives of hundreds, or thousands, or possibly millions of patients globally. Every now and then I catch myself humming one of my favorite Paul Simon songs. He may not have been thinking of ophthalmic advances when he wrote the words “these are the days of miracle and wonder… medicine is magical…these are the days of lasers in the jungle. Lasers in the jungle somewhere…” but I smile to myself knowing firsthand just how true the lyrics are.