For years the Holy Grail of ophthalmology has been to give patients the ability to see clearly both and near and far distances. Verne Sharma, CEO of Calhoun Vision, thnks his company’s light-adjustable lens has reached that goal.
The LAL device uses a unique blend of light-sensitive polymers to create a customized lens to correct astigmatism, myopia and hyperopia. Sharma told MassDevice.com recently that the Calhoun Vision has developed a way to also treat presbyopia.
Called "adjustable blended vision," the technique calls for 1 eye to be corrected for far vision and the other eye to be corrected for nearsightedness, Sharma told us.
"Now here we have 2 eyes we are working with, 1 eye set up beautifully for distance and the other eye, with this extended depth of field. We can very precisely give each patient, customized to their own needs, this extended depth of field, so we get great near vision," he explained.
In Boston recently for the annual American Society of Cataract & Refractive Surgery conference, Sharma sat down with MassDevice.com to explain the technology behind the groundbreaking lens and how Calhoun Vision aims to disrupt ophthalmology with its LAL. Following is a transcript of our chat, edited for clarity.
MassDevice.com: Can you give us a short backgrounder on Calhoun Vision?
Verne Sharma: The company started off in 2000 with the idea that had been conceived several years before, that the best way to get to a level of a predictability in the outcome of a cataract procedure is to be able to adjust the power of the lens, after the lens had been placed in the eye.
The world is changing, and more and more people do not want to wear glasses after a major procedure like this. So a new category of technology has been born to respond to this need for glasses-free vision after cataract surgery. That has led to new optical designs like multifocal lenses or accommodating lenses. It has led to new materials such as advanced acrylic materials, advanced silicone polymers and combinations thereof. There have been new clinical procedural techniques and new equipment.
Many advances have occurred, but one fundamental problem continues to exist, which is that despite all of these technological advances, you cannot put a lens in a patient’s eye and predict where the lens is physically going to end up in the eye because the eye heals and the healing process is very variable.
Our company was developed on the idea that we wouldn’t try to put a lens in and hope that somehow it would end up in the right place as the doctor expects. Our idea is we can relax about the biometry, we do not have to worry about astigmatism because you can treat it and let the wound healing process cause the lens to move or shift to wherever you want to end up in the eye. At the end of this healing process, we’ll simply come back and change the power afterwards.
We do so by shining a certain light of a certain wavelength onto the lens inside the eye and then changing the power quite precisely. It is a very different way to do things. It’s a huge departure from the norm and is very transformational – that you could put a lens in the eye, get it closed, and then bring the patient back when the eye has healed, typically about three weeks later. Simply re-measure the patient’s vision and then correct the power of that lens to that patient’s exact prescription. It’s a huge sea change in the business.
MassDevice.com: How precisely does that work?
Verne Sharma: Our lens has a matrix that is cross-linked. We found the right cross-link density is not so loose that the lens is floppy and flexible and will collapse; the lens has to have a certain mechanical integrity so it sits inside the eye and doesn’t fall. On the other hand, if it’s too stiff, you can’t fold it and put it through a small incision.
We found the right mechanical cross-link in density to use in this lens that gives it the right mechanical and optical properties, but at the same time is fairly loosely cross-linked so you can have mobility of other materials in the lens. These materials that are mobile are lower molecular weight, short-chain monomers. We label them macromers, because they are slightly bigger than is typical – their molecular width is about 10,000 compared to the base polymer which has a molecular width of 200,000.
The base polymer is fully polymerized, perfectly stable, not capable of any further reaction. The macromers are the "juice" in our material. They are homogenously dispersed throughout the lens mass and they’re perfectly mobile. If a patient comes in and we put a 20 diopter lens in their eye, after the eye heals the patient comes back and the doctor measures their vision and says, "Oh, you know, I should have put a 21 diopter lens in this patient’s eye."
Now we need to add one diopter of power. Today he would prescribe glasses, right? One diopter, easy. In our case we simply shine a light selectively on the central part of the lens and, because there’s a catalyst in the lens which is specific to the wavelength of light that we use, the light causes the catalyst to break up into reactive molecules and they cause these little macromers to link together and become polymerized. You are removing the macromers by polymerizing those that are in the path of the light. That creates a concentration disequilibrium with macromers massed on the periphery of the lens and none where the light struck.
To re-equilibriate the concentration throughout the lens mass, now you have this movement of these molecules through this matrix. They are mobile enough and short-chained, so they can pass through and they physically diffuse into the central part of the lens. So you move macromers from the periphery into the center and you cause the center to swell and that swelling adds power.
What we have developed is this unique ability to figure out how much light we put in the center, of what intensity, for what duration, how long, how wide should the beam be, and what the profile of the light should look like to have a very smooth transition between the treated and untreated part of the lens. You don’t create bumps and aberrations that didn’t exist before.
We have this way of creating a very small transition from the area where we concentrated the light to the untreated part of the lens, so as to create a very smooth fall-off and a very smooth, controlled shape change. The mechanism of action involves a shape change, a change in the raise of curvature of the lens, not refractive index. Many people think that we change the refractive index; we don’t.
The patient can now participate in their own care. They can tell the doctor how well they are seeing. Let’s suppose they come back and say, "You know, Doc, I’m not seeing quite well enough a distance."
Maybe you take away a little of the power so the doctor added one diopter. Let’s suppose he needs to take away half a diopter, what he would do is he would then irradiate selectively the outer part of the lens, draw molecules away from the center, flatten it and therefore take away power. As long as there is macromer remaining in the lens, the doctor can move, he can enhance the procedure back and forth until the patient is happy. Then he performs a final lock-in step that locks or polymerizes all the macromers and freezes them in their current spot, so no more movement and therefore shape change is possible.
MassDevice.com: How do you ensure that the UV light doesn’t damage other parts of the eye?
Verne Sharma: That’s a good question. Several ways. One is that built into the lens itself are some UV blocking agents that absorb UV light. We have to combine adequate blockage with allowing the light to do its work, right? The challenge in the early days of the discovery of the optimized lens formulation was what is this ideal mixture of UV blocking agent, photo initiator, macromer and base polymer? That’s what our patents are built around. The first order of business is to provide enough blocking capability so the patient could go out, drive to the grocery store, go collect their meal or whatever it may be, and have enough protection so that UV light in the visible spectrum doesn’t prematurely cause a chemical reaction to kick off. We needed enough UV agents in the bulk to give us 2, 3 hours of short-term protection, but we didn’t want to put so much in there that it would compete with the photo initiator to cause a chemical reaction to take place.
We cut back on UV in the bulk, because we then decided to put a UV blocking agent in the back layer, in the back of the lens, mold it seamlessly onto the optic that’s rich in UV blocking agent. Now it’s at the back of the lens so it doesn’t interfere with the photo chemistry, but it blocks light from going to the back of the eye.
That’s how we protected the retina from UV light that’s striking lens, both in terms of short term UV protection in the bulk of the optic but also a back layer that ultimately attenuates or blocks all light from going to the back of the eye.
MassDevice.com: You’ve been on the market in Europe since 2008. What’s your status on the path to U.S. approval?
Verne Sharma: We got CE Mark approval in 2007, based on clinical trial. The European philosophy is a lot different from the FDA. The Europeans say, "The fundamental aspect of a new technology that we want to ascertain its safety. The market will decide on efficacy. If it’s safe, we can release it to our populace, our patients. We can protect their good health, but whether it works or not, the market will decide. If it doesn’t work, it won’t survive. If it works, great."
I wish the FDA would take the same position, but they don’t. We launched in Europe in 2008 and have been selling ever since. We’ve sold roughly 3,500 lenses in Europe in our 5 years to date. The study in the U.S. is 600 eyes, of which 400 are LAL eyes and 200 are a control lens. This control lens is a previously approved monofocal lens of the doctor’s own choosing. We don’t tell the doctor which monofocal lens to choose. They pick the ones that they are most comfortable with, that they get the best results with and where the (A) constant and other factors that impinge upon their selection, they have worked out over the course of time.
We are authorized to use 18 sites across the country. We have selected 15 already. We had the good fortune that there was a lot of interest in the technology.
We’ve now enrolled 300 patients, so we are more than ⅓ of the way through. Our plan is to complete the enrollment by the end of this year and then follow the patients for a year, and therefore make a submission in early 2016 to the FDA.
MassDevice.com: Can you give me a sense of outside-the-U.S. revenues on an annual basis?
Verne Sharma: Our strategy in going to Europe was several-fold. We knew in 2008 that there had been some companies before us that had launched in Europe and failed, and in fact had some catastrophic experiences. Part of that was launching with a view to already going after revenue, as opposed to going after other goals or objectives. We wanted to go to Europe with a view to achieving a few key things.
One was how we would treat those patients – could we reproduce in the commercial setting what we were seeing in the more controlled clinical studies? That was important. Secondly, we really wanted to try to get some detail published, to begin to show the world what we could do. And we also wanted to learn what it would take, how could we as a small company learn the vagaries of the business? Could we price our product appropriately? How would the competition respond? How would doctors integrate this modality into their practice? Would our capital equipment, our light delivery device, stand the test of repeated use? Was it robust enough? Lots to learn. Revenue was not our number 1 priority.
Our strategy, as a small company of limited bandwidth that was working through distributors, was to choose a small group of doctors, support them adequately and make sure they got good results, because good results tell a story. We were able, over the course of the last several years, to collect a small cadre of really good, serious people who feel strongly about the technology, are good communicators. Over the course of time, we’ve really controlled our roll-out to try to make sure that we could work closely with these doctors.
Our sales have generally varied around the $500,000 mark. When we launched in Europe, I told the board that we are not in Europe for the business of trying to greedily go after wherever we could sell. That would be a mistake. Our strategy was to listen, to learn, to adapt, to figure out what we could do better and differently and set the stage for subsequent commercialization in Europe and indeed for getting ready for the U.S. market.
MassDevice.com: What can you tell me about the financing of the company, venture capital rounds, anything like that, how much you’ve raised to date?
Verne Sharma: We’ve raised close to $80 million from private individuals. We have no institutional capital in the company today.
We had no trouble financing the company over the years. We’ve raised $80 million purely by people writing checks. The only downside of that is that it takes a lot of the CEO’s time, that you have to talk to a lot of people and answer their questions and so and so. It just take a lot of time.
Our strategy has been to raise enough money to get us to another meaningful milestone, and then you raise more at a higher valuation, because you can make the claim legitimately that the company is better off and has de-risked some elements of its business. We haven’t had a down round from the B round onward, we are now at F. We now want to go to an institutional round of investments. It’s time to bring in a large bolus of money to take us through the next 3 years, so we’ve hired an investment banker, Piper Jaffray.