INNOVATION IN RETINA

Edited BY Emmett T. Cunningham JR, MD, PhD, MPH, and Pravin U. Dugel, MD

Daniel M. Schwartz, MD: UCSF and Caltech

Successful innovation in an academic setting.

Jerry Helzner, Senior Editor

As any regular reader of this column will know, almost all of the highly successful ophthalmic innovators previously featured here followed a similar path to success by forming private sector start-ups, typically financed by wealthy individuals or large venture capital firms, or both.

Daniel M. Schwartz, MD, professor of ophthalmology at the University of California San Francisco (UCSF), has gone in a different direction. For the last 15 years, he has been the primary point person in marshalling an array of impressive brainpower from both UCSF and California Institute of Technology (Caltech) to develop a stunning array of advanced ophthalmic concepts. These high-potential initiatives include the unique Calhoun Light-Adjustable IOL (already successfully commercialized in Europe), a new type of corneal cross-linking that uses safer visible light rather than UV light, a form of OCT angiography that could replace invasive, higher-risk fluorescein angiography procedure, and two early stage glaucoma-related projects.

The Calhoun LAL is unique in that it can be adjusted by nearultraviolet light after it is placed in the eye.

DRAWING UPON TOP SCIENTISTS

While one might expect that innovating in an academic setting would involve such major obstacles as bureaucracy, extensive oversight, complicated licensing agreements, and research budget constraints, Dr. Schwartz says that he found no such impediments to success. Asked to enumerate the advantages and disadvantages of innovating in academia, Dr. Schwartz quickly replies: “I have found no disadvantages.”

In terms of advantages, he cites the ability to tap into the prodigious expertise in many disciplines embodied by the faculties of UCSF and Caltech. A prime example of this talent pool is the team that developed the Calhoun lens, a breakthrough IOL whose power can be fine-tuned after it has been implanted in the eye. For the advanced knowledge of chemistry, chemical engineering and polymer materials needed to make the Calhoun concept a reality, Dr. Schwartz enlisted Robert Grubbs, PhD, a Nobel laureate in chemistry from Caltech, and Julia Kornfield, PhD, a professor of chemical engineering at Caltech.

Dr. Schwartz believes the drivers of the most successful ophthalmic innovation are clinicians who discern an unmet medical need and have some basic ideas on how to meet that need. “What we are doing here is translational research,” Dr. Schwartz says. “We first identify an idea with potential and then draw upon the two university faculties to create a team of scientists who can contribute to the development of a successful device or therapy.”

A ‘PEDIGREE’ FOR INNOVATION

If anyone has the background to act as a sparkplug for ophthalmic innovation, it is Dr. Schwartz. The son of a distinguished California retinal specialist who served as a role model, young Dan also got to experience the patient’s perspective first-hand when, as a medical student, he received bilateral corneal transplants as a result of a severe case of keratoconus. Having his own eyesight threatened and then saved through medical intervention served as a motivating force in his career choice.

“In addition to having my father as a great role model and going through the transplant procedure myself, I also had a wonderful mentor in Dr. John Baxter, an endocrinologist and UCSF pioneer in biotechnology,” he says.

DEVELOPING THE CALHOUN LENS

Like most innovators, Dr. Schwartz did not enjoy immediate success. One of his early ideas was a drug design using thyroid hormone analogues to treat glaucoma. Though the concept was licensed, it was eventually dropped. However, this initiative did represent Dr. Schwartz’s first collaboration with non-ophthalmic scientists — a model that was destined to be expanded for later initiatives.

When Dr. Schwartz began to think about the possibilities of a light-adjustable IOL in the mid-1990s, he quickly set down three clinical parameters that had to be met to have any chance of success. The lens adjustment had to be capable of correcting errors of 2.00 D or less, the adjustment procedure had to take place quickly, and the adjustment procedure had to be safe. By bringing Drs. Grubbs and Kornfield into the project, he had the necessary expertise to bring the concept to fruition.

“The Calhoun lens does encompass a complicated technology,” Dr. Schwartz says. “We worked with post-docs and conducted pre-clinical studies. We were fortunate to receive substantial funding from ‘angels’ in the Los Angeles area.”

Currently, the Calhoun (named after the street Dr. Schwartz lives on) light adjustable lens has European approval, some limited sales on that continent, and has been praised in several studies presented at recent ARVO meetings.

“I’m not surprised it is taking so long to obtain FDA approval for the Calhoun lens because it is a breakthrough technology that requires thorough evaluation,” says Dr. Schwartz. “We are currently in phase 3 US trials to treat sphere and cylinder.”

THE COLLABORATION PROCESS

When Dr. Schwartz or a colleague comes up with an idea, the first step is often to go to Caltech with it.

“We want the Caltech scientists to first tell us if they believe the idea is feasible,” Dr. Schwartz says. “Then, we want to know if we can obtain the seed money to pursue it. One great advantage we have in our situation is that all the resources we need to pursue an idea are at our disposal as part of this collaboration between UCSF and Caltech.”

Dr. Schwartz emphasizes the importance of his continuing to see patients because it keeps him involved in clinical practice and helps him identify more areas in which he can invent and innovate.

THE UNIVERSITY’S ROLE

As a full-time member of UCSF department of ophthalmology, Dr. Schwartz is comfortable with the fact that the university holds the patents to innovations developed in the institutional setting.

“Lawyers handle the negotiations between the university and the innovators, who become the licensees,” he notes. “It works out well if everyone plays by the rules and potential conflicts of interest are managed.”

One of the key initiatives to be spawned from the UCSF/Caltech collaboration has been a semi-annual joint symposium in which innovators from any medical specialty or discipline can present their ideas.

“The symposium is attracting more attention and we could expand it to bring in other universities,” says Dr. Schwartz. “We would also like to attract additional financing to fund some of the innovations we are generating.” RP