REFINING RETINA: LESSONS FROM THE MOUSE

By Pravin U. Dugel, MD and Emmett T. Cunningham, Jr., MD, PhD, MPH

In the inaugural Innovation in Retina column in September 2010, we suggested that the subspecialty of retina was poised for major, disruptive change. We quoted Malcom Gladwell, who wrote, “In the end, Tipping Points are a reaffirmation of the potential for change and the power of intelligent action. Look at the world around you. It may seem like an immovable, implacable place. It is not. With the slightest push — in just the right place — it can be tipped.” Indeed, our retina world has been “tipped.” But what’s next?

More recently, Gladwell penned a fascinating piece for The New Yorker, in which he suggested that most major technological and scientific advances are “invented by multiple, separate people over a relatively short span of time.”¹ In exploring this concept, Gladwell took the invention of the computer mouse as an example and challenged the commonly held notion that Steve Jobs “stole” the idea of the mouse from Xerox PARC. While PARC did show Jobs that idea, much of which was actually copied from Doug Engelbart at the Stanford Research Institute, it was the implementation that mattered, and Jobs and Apple, along with Ideo, had to work hard to take the idea of the mouse — which in the Xerox version cost hundreds of dollars and was fragile — and make it accessible, reliable and easy to use for the masses. Gladwell wrote:

“The difference between direct and indirect manipulation — between three buttons and one button, three hundred dollars and fifteen dollars, and a roller ball supported by ball bearings and a free-rolling ball — is not trivial. It is the difference between something intended for experts, which is what Xerox PARC had in mind, and something that’s appropriate for a mass audience, which is what Apple had in mind. PARC was building a personal computer. Apple wanted to build a popular computer.”¹

What does this have to do with innovation in retina? In our opinion, we are witnessing a transition from defining to refining treatment of chronic retinal diseases – from ‘three buttons to one,’ if you will. The ‘definition’ emerged from the realization that neovascular AMD, retinal vein occlusion, and diabetic retinopathy share a core common pathway consisting of increased permeability and angiogenesis, largely, although not entirely, mediated by VEGF-A, and that significant therapeutic benefit can be achieved through chronic VEGF-A inhibition. The refining will come by way of improved delivery, be it sustained release, gene therapy, or a currently unrecognized route; and by improved outcomes through targeted combination therapy, such as PDGF inhibitors among others.

Through the generous support of Regeneron, we present here the collected Innovation in Retina essays published in Retinal Physician since 2010. Many of the most influential innovators in retina are highlighted in these pages. Future issues will introduce yet others who are redefining retina. ■