“Innovation distinguishes between a leader and a follower.” — Steve Jobs

Unlike invention, innovation uses an invention to solve a problem. Innovators see things differently and change our society with their visions. In retina, we have had some major innovators, and I am pleased that in this issue we highlight one of the key innovators in retinal vascular disease, Napoleone Ferrara, who has been awarded both the Lasker Award and the 2014 Champalimaud Vision Award for purifying, sequencing, and cloning vascular endothelial growth factor (VEGF) in 1989. In 1992, his lab first described fms-like tyrosine kinase-1 (Flt1) better known as VEGF receptor 1, and in 1997 they developed a mouse monoclonal antibody to VEGF-A that we now know as Avastin. Without his pioneering work, our treatment of retinal vascular disease would be very different!

Almost 50 years earlier, ophthalmologist I.C. Michaelson described a secreted “factor X” that caused abnormal vascular growth and leakage. In the 1970s, the father of angiogenesis, Judah Folkman, MD, identified tumor angiogenesis factor and for the first time described the idea that angiogenesis was required for tumor growth. In 1983, doctors at Harvard Medical School isolated vascular permeability factor (VPF). Later, VPF was found to be the same molecule as VEGF, and the search for factor X had been completed. During my residency in the early 1990s, I was honored to collaborate with many other innovators at Massachusetts Eye and Ear Infirmary working to elucidate the role of VEGF in ocular disease, including Joan W. Miller, MD, Anthony P. Adamis, MD, Lloyd Paul Aiello, MD, PhD, Lois Smith, MD, PhD, and others. Their body of work laid the foundation for the use of anti-VEGF agents, which has truly changed our profession.

Interestingly, the first company to use this knowledge — Eyetech Pharmaceuticals — was started by ophthalmologists David Guyer, MD, Samir Patel, MD, and Dr. Adamis, and the first approved anti-VEGF treatment was Eyetech’s pegaptanib sodium injection (Macugen). Later, the pivotal Lucentis Phase 3 trials, MARINA and ANCHOR, showed for the first time improved vision in wet AMD patients. Thereafter, every few years, we have had an evolutionary improvement in the technology, such as with Eylea (Regeneron) and Lumitin (Chengdu Kang Hong Biotech, in China). Now, we are learning the results of brolucizumab (Novartis) and abicipar pegol (Allergan/Molecular Partners). Hopefully, the bar will continue to move forward.

In this issue, we also look at another innovator in Cedric Francois, MD, PhD, a transplant surgeon with particular expertise in immunology who started 2 companies with the goal of moving the bar forward in dry AMD. His latest product, APL-2, is the first complement inhibitor to have significantly reduced GA progression in a phase 2 study. Fortunately, our profession is blessed with innovators like these who can push us forward. RP