Power Adjustments: Potential of the LAL

Calhoun Vision, Inc., of Pasadena, California, was founded in 1997 based on the concept of the Light Adjustable Lens (LAL). Conceived by ophthalmologist Daniel Schwartz, MD, of the University of California, San Francisco, and Robert Grubbs, PhD, a chemistry professor and Nobel laureate (2005) at the California Institute of Technology, the LAL was designed to allow power adjustment of the lens after implantation, with the noninvasive application of light.

The concept had immediate appeal to cataract surgeons worldwide, who realized that adjusting the refractive properties of the lens postoperatively would allow them to minimize or eliminate residual postoperative refractive error. The product received the Conformité Européenne (CE) Mark in 2007 and was introduced commercially in Europe the following year. CRST Europe spoke to Calhoun’s president and chief executive officer, D. Verne Sharma, about the current state of the LAL and Calhoun Vision, how he sees the LAL fitting into modern ophthalmology practice, and where he sees the technology and the company going.

CRST Europe: You had a history in ophthalmology before Calhoun Vision. Please tell us about that.

Sharma: My experience in ophthalmology goes back to 1996, when I joined Summit Technology, the laser company that received the first US Food and Drug Administration (FDA) approval for PRK and subsequently for LASIK. I was the president and chief operating officer at Summit for 4 years, until the company was sold to Alcon Laboratories, Inc. (Fort Worth, Texas) in 2000. I was involved in the commercial introduction of PRK and then LASIK into the market, including training the surgeons in the clinical procedure and, perhaps more challenging, in how to commercialize this new technology. We were introducing a realm of refractive surgery to succeed and replace radial keratotomy, and this required us not only to teach the doctors how to perform it in the clinic, but also how to market the procedure to a new demographic: younger people opting for an elective procedure. That was an important education for me and for all of us who were involved at the time. It set the stage for the work I am doing at Calhoun, which is to introduce another novel breakthrough technology in the field of vision care, the LAL.

CRST Europe: You started with Calhoun when the LAL technology was still in its infancy, correct?

Sharma: I joined Calhoun in 2001 as CEO, and I was here for 2 years. I left in 2003 because there was still a lot of scientific and technical work to be done and the company needed a technical leader, more a chief technology officer than a CEO. At that time, the company hired a technically adept scientist to succeed me. I returned in April 2008 as Calhoun was getting ready to launch the LAL commercially in Europe.

CRST Europe: What is the current regulatory and market status of the LAL in Europe?

Sharma: The LAL received the CE Mark in 2007, and we began selling it in Germany in May 2008. We have since expanded to five more countries in Europe: Spain, France, Italy, United Kingdom, and the Czech Republic. Our biggest base of users remains in Germany. We have distributors in each country that have been involved in the introduction of many modalities, both in LASIK and IOL technology. Most, if not all, have experience with capital equipment and disposables. Because our system of therapy involves a light-delivery device, which is a specialized piece of capital equipment, as well as the lenses themselves, we needed distributors who had facility with both capital equipment and IOL sales.

CRST Europe: The CE Mark approval is Europe-wide. When do you plan to introduce the LAL in other markets?

Sharma: We are addressing the countries where the vast majority of IOLs are being implanted, and certainly the countries where the premium IOL technologies available today are being used. Our LAL technology is aimed at the premium demographic, meaning those who are willing to pay out of pocket. These patients exist in many other countries, and we would like to bring our technology to them. The LAL has also been introduced in Canada where it is being clinically studied. For the moment we are less interested in uncontrolled expansion and more focused on working with a limited number of doctors in a managed rollout. This allows us to get good feedback at this early stage of commercializing the technology.

Our current strategy in Europe is to work with selected doctors to understand the issues that affect the early adoption of the technology. Are there clinical issues that require the fine-tuning of the technology? What marketing programs can we put in place? What is the message that best resonates with our desired market demographic? Is our light-delivery device sufficiently reliable in the field? Those are questions we are interested in learning about and answering. So we are working with a limited number of doctors, with the aim of attaining excellent clinical results and receiving high-quality follow-up and feedback on the technology and the related marketing and economic aspects.

Our eventual objective is to be the leader in the field of premium IOLs, but we are purposely starting off in a managed and controlled manner. We want to make sure that the early experiences of doctors are positive. We’ve seen examples of technologies that were brought to market but did not succeed, ultimately because the initial experience was less than favorable. We want to make sure that we can support our doctors and ensure that they are adequately trained and effectively supported in their marketing programs, that we answer their questions quickly, and that we meet their service needs responsively and competently.

CRST Europe: The LAL technology is new. Are you dealing mostly with opinion leaders at this point?

Sharma: No; we want a broad cross-section of customers in our mix. We do not want to be perceived as a technology that is suitable only for extremely well-trained surgeons or high-volume practices. We want the technology to be appealing to and accessible for any patient who desires superior visual outcome. Our users in Europe are a good mixture of key opinion leaders, academic centers, busy refractive cataract surgeons who can integrate this technology successfully into their practices, and young surgeons who will be among the next generation of leaders in ophthalmology.

CRST Europe: How is the LAL performing clinically?

Sharma: Our experience after more than 2 years in the European market has taught us that cataract patients value crisp distance vision. This means that surgeons are looking to us to deliver refractive accuracy. We are able to respond to this with the LAL because we can precisely correct residual refractive error after the cataract is removed and the eye is stable. Our results in clinical studies and in commercial practice demonstrate that we can repeatably eliminate residual refractive error of up to ±2.00 D of spherical correction with or without 2.00 D of preexisting or surgically induced cylinder. The lens is implanted like any other IOL, through a small incision using an injector. The patient returns 2 weeks postoperatively, after the eye has healed, so that the doctor can remeasure the refraction and then make the appropriate correction. The beauty of this technology is that surgeons need not be unduly concerned about the three major causes of residual refractive error: errors in biometry, preexisting or surgically induced cylinder, and the unpredictable effect of wound healing. We know that any residual error will show up in that 2-week period after implantation and prior to adjustment.

In clinical practice today, power adjustment is often required once, but it can be done twice and even a third time if the doctor wants to fine tune before he or she delivers the final lock-in treatment. But for each subsequent treatment the effect is less because the amount of available macromer is reduced. Every time the lens is adjusted, macromer is consumed by the photopolymerization reaction, and therefore there is less macromer to bring about further power change.

Ultimately, once the patient is happy, the surgeon must lock in the lens power to make sure that prolonged uncontrolled exposure to sunlight does not cause undesired change. Until the lock-in, the patient must wear ultravioletprotecting sunglasses that we supply, both indoors and out, to make sure that no premature photopolymerization takes place. Patients have been good about complying.

CRST Europe: It has been said that the technology is capable of correcting higher-order aberrations (HOAs).

Sharma: The spatial resolution of the material and the pattern of light generated by the digital mirror device are so precise and flexible that we can create any shape on the lens. We have demonstrated in the laboratory the ability to correct HOAs. So yes, the use of aberrometry in conjunction with this lens to correct HOAs, the removal of which would enhance the patient’s vision, is something we believe we can do clinically. In fact, this is part of one of our approaches to presbyopia correction that I want to tell you about later.

CRST Europe: When do you see expanding distribution geographically beyond Europe?

Sharma: Calhoun is a relatively small company, and our bandwidth is not unlimited. While we are interested in expanding geographically, we want to do it in a controlled way so that we can adequately support our distributors and doctors. We plan in the future to apply for regulatory approval and enter markets in Latin America and Asia.

We have started clinical work in Canada, and we are pursuing marketing clearance in Mexico. Both markets are important because of their size, high quality of cataract surgeons, and proximity to the United States. We have completed phase 1 and phase 2 studies for FDA approval. With more than 1-year follow-up of the 74 patients in phase 2, we exceeded all efficacy endpoints and met all of the safety endpoints that the FDA established for the trial. The investigators are happy with the results. We are now in discussions with the FDA concerning the commencement of phase 3.

CRST Europe: Can you review the results to date?

Sharma: The site in Europe that has the most commercial experience is Bochum, Germany, the Ruhr Valley Center for Vision Science. Professor Burkhard Dick and Dr. Fritz Hengerer have treated close to 300 eyes with the LAL. They have published a number of papers,^1-3 including 1-year results in 21 eyes, and they have presented a series of 110 eyes followed for 1 year, in which 86% of patients with the LAL see 20/20 or better uncorrected at distance. That is a phenomenal result, more reminiscent of LASIK than any other kind of IOL. It really speaks to the precision with which we can correct astigmatism and defocus. In that same series, 99% of eyes were within ±0.50 D of defocus equivalent target refraction compared with 46% prior to adjustment. This kind of result has been repeated by other surgeons using the LAL commercially across Europe, even in postrefractive surgery eyes and long and short eyes. We are gratified to see that the repeatability and accuracy is holding up across multiple sites. This is why our technology has a strong future. A cataract surgeon is unlikely to offer an advanced technology IOL, for which he or she charges patients a significant premium to get a better refractive outcome, if he or she is not confident that it can routinely deliver that outcome. A big part of what we offer is predictability because the response of the lens to postoperative adjustment is so precise.

CRST Europe: You mentioned correction of presbyopia.

Sharma: We are exploring three ways to deliver good UCVA at near and intermediate distance, in addition to far. One is a variation of monovision that we call adjustable blended vision. Because the doctor has such fine control over the final refraction with this light-adjustable technology, he or she can now be assured of getting the desired result in both the dominant and nondominant eye. This means the surgeon can target one eye for plano and the other for, say, -1.25 D, and he or she can adjust it until the patient is happy. If the patient does not adapt well to monovision, the surgeon can undo the myopic effect in the nondominant eye and target it for plano at distance. This allows the surgeon to simulate for the patient what near, intermediate, and far vision would be like with the blended vision approach. We can do this with our technology, and no one else can, because the lens can be adjusted after implantation to a desired refraction. Second is customized near add, in which a zone of near add power is created in the central part of the lens. The size of the zone and the amount of add power can be customized to patients’ visual needs and anatomy, particularly their photopic pupil size. This approach has been studied in 80 eyes in Mexico by Dr. Arturo Chayet and in Spain by Professor Pablo Artal and his scientific and medical team. We have begun a limited commercial rollout in Germany and France and will shortly do the same in Spain. The addition of multifocality to the lens is characterized by a smooth transition from the rest of the lens into the add zone, a key feature of the technology. The ability to customize the size and power of the add zone allows the surgeon to match the treatment to the individual needs of the patient. The third approach is to add a controlled amount of spherical aberration to the lens to provide extended depth of focus. We can offset the existing spherical aberration in the cornea and lens and add a controlled amount of additional negative spherical aberration. This can provide excellent near and intermediate vision without compromising distance vision or introducing significant loss of contrast sensitivity. This adaption of the use of spherical aberration takes advantage of the technology’s ability to change the shape of the lens’ refractive surface. Clinical studies of this application have been under way for some time and have yielded excellent results in terms of near and intermediate UCVA in the patients treated to date.

CRST Europe: What do you see for the future of Calhoun?

Sharma: Our strategy is to create a valuable company by having a demonstrably superior product, by attaining FDA and other regulatory approvals around the world, and by working with doctors who enthusiastically support the product and use it preferentially in their premium practices. Those are important metrics of success, and by staying focused on accomplishing those things, and hence creating a highly valuable enterprise, the future will take care of itself.

D. Verne Sharma is CEO and President of Calhoun Vision, Inc. He may be reached at e-mail: vsharma@calhounvision.com.

1. Hengerer FH,Hütz WW,Dick HB,Conrad-Hengerer I.Combined correction of sphere and astigmatism using the lightadjustable intraocular lens in eyes with axial myopia.J Cataract Refract Surg.2011;37(2):317-323.
2. Hengerer FH,Conrad-Hengerer I,Hütz WW,Dick B.[Adjustment of sphero-cylindrical refractive errors in hyperopic eyes:6- month results after cataract surgery and implantation of a light-adjustable intraocular lens].Klin Monbl Augenheilkd. 2010;227(9):729-34.Epub 2010 Jun 23.In German.
3. Hengerer FH,Conrad-Hengerer I,Buchner SE,Dick HB.Evaluation of the Calhoun Vision UV Light Adjustable Lens implanted following cataract removal.J Refract Surg.2010;26(10):716-721.Epub 2010 Apr 15.