The Calhoun adjustable IOL breaks new ground

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1 Page 1 of 5 Article Date: 3/1/2014 Focus on Cornea The Calhoun adjustable IOL breaks new ground Chemical technology allows the lens reshape itself to produce precise outcomes after implantation. BY JERRY HELZNER, SENIOR EDITOR What do a Nobel laureate in chemistry and a professor of chemical engineering from the California Institute of Technology have to do with developing a new type of intraocular lens? The answer is, almost everything. That s because the unique concept behind the Calhoun Light-Adjustable-Lens is to produce a chemical reaction that changes the shape of the lens which allows it to be adjusted once it is already in the eye. The brainchild of Daniel Schwartz, MD, a retina specialist and professor at the University of California, San Francisco (UCSF), the development of the Calhoun LAL (named after the street Dr. Schwartz lived on in San Francisco) is noteworthy because it has encompassed a multi-disciplinary approach in an academic setting. This collaborative path to innovation is considered unusual in an era when start-up ophthalmic companies financed by deeppocketed venture capitalists abound. So far, the approach has resulted in approvals for the Calhoun LAL in most European Union countries and Mexico, places where the lens is now in everyday use. It has also had positive reviews in independent studies, including one study involving post-refractive patients, a group with surgically altered corneas for whom it is difficult to achieve target outcomes in cataract surgery. PATH TO THE US MARKET Navigating the FDA The big test may come late in 2015, when Calhoun Vision (Pasadena, Calif.) seeks FDA approval of an IOL different than anything the FDA has seen before.

2 Page 2 of 5 The Calhoun LAL lens assumes its final shape when biocompatible macromers sensitive to UV light are irradiated, causing a chemical reaction in the treated macromers. We will be seeking approval in the category of an astigmatism-correcting lens, says Robert Maloney, MD, chief medical officer for Calhoun Vision. "The Calhoun lens is adjustable, but there is no FDA pathway for adjustable IOLs. The pre-set pathway the FDA offers to approval is as a toric lens." Developing the Calhoun concept The most compelling aspect of the Calhoun lens is that its power can be adjusted once it is in the eye and the eye has healed. When Dr. Schwartz began to think about the possibilities of a light-adjustable IOL in the mid-1990s, he determined it had to meet three clinical parameters to have any chance of achieving success: The lens adjustment had to be precisely capable of correcting spherical and/or astigmatic errors of 2.00 D or less. The adjustment procedure had to happen quickly. The procedure had to be safe. For the advanced knowledge of chemistry and chemical and polymeric engineering, Dr. Schwartz enlisted Robert Grubbs, PhD, a Nobel laureate in chemistry at California Institute of Technology Caltech and Julia Kornfield, PhD, professor of chemical engineering at Caltech. With Drs. Grubbs and Kornfeld, Dr. Schwartz had the expertise to bring the concept to fruition. The Calhoun lens does encompass a complicated technology, Dr. Schwartz says. We also worked with post-docs and conducted pre-clinical studies. What makes the lens adjustable The LAL is similar in many respects to standard monofocal IOL; surgeons can implant it into the eye using their customary surgical technique. What makes the LAL different are special biocompatible materials, called macromers, incorporated into its makeup. These materials are sensitive to ultraviolet light of a certain wavelength. When the light irradiates them, the macromers undergo photopolymerization. This subsequently leads to a predictable change in the shape of the surface of the LAL and hence, its power.

3 Page 3 of 5 Dr. Maloney says one adjustment is all most Calhoun recipients require. We wait a few days to assess the results of the adjustment, he says. If a second adjustment is needed, it can be done. PHASE 3 TRIAL UNDER WAY 600-patient study In the United States, the Calhoun LAL has successfully completed phases 1 and 2 of the required clinical investigation. The third and final phase of the study has begun and will expand to 15 locations across this country. We are about one-quarter of the way through our phase 3 enrollment for a 600-patient study, says Dr. Maloney. We hope to complete enrollment by late summer. More than 150 patients have already been implanted with the lens as part of the study. Patients who receive the Calhoun lens will be followed for one year, leaving open the possibility for a fall 2015 submission to the FDA, Dr. Maloney says. Here, a patient who had been implanted with the Calhoun LAL is undergoing the adjustment process to achieve the desired refractive outcome. COURTESY: CALHOUN VISION Communication with the FDA is key Because the Calhoun LAL is different than any IOL the FDA has ruled on, Dr. Maloney says the company is making sure the agency has all the information about the unique qualities and capabilities of the lens that it needs to make a decision. This element of the approval process takes on added importance because Abbott Medical Optics recently ended development of the next-generation accommodative Synchrony lens. David Chang, MD, who was medical monitor for the Synchrony clinical trials, recently stated that the Synchrony got stalled in the FDA approval process primarily because the FDA has no real definition of what constitutes an accommodative IOL on which to base a decision. We are confident that the FDA understands the Calhoun lens, says Dr. Maloney. Though there is no FDA pathway to approval for adjustable IOLs, there is a well-defined pathway for approval of an astigmatism-correcting lens. Our phase 3 study design is to prove the Calhoun s capabilities as a toric lens, but we hope it also proves the lens is just as effective with patients with spherical errors who do not require a toric lens. THE MULTI-MILLION PATIENT MARCH Post-refractive patients: a key market Many individuals who had laser refractive surgery in the 1990s are now showing up as candidates for cataract surgery. They represent the vanguard of what one cataract surgeon has described as a multi-million patient issue. These patients present a problem to

4 Page 4 of 5 surgeons because achieving accurate IOL calculations in post-refractive eyes is difficult despite efforts to upgrade calculation formulas and introduce new technologies. We also know that post-refractive patients have already made a previous commitment to excellent vision. They will expect an equally excellent outcome from their cataract surgery, says Dr. Maloney. In studying the effectiveness of the Calhoun LAL in post-refractive cataract surgery, Lawrence Brierley, MD, of Victoria, B.C., was able to find 34 post-refractive eyes in 21 patients out of a 437-eye retrospective study of the Calhoun lens. 1 In the post-refractive eyes, adjustment began two weeks after the initial lens implantation, with patients receiving one, two or three adjustments to achieve target final manifest refraction spherical equivalent. In the final measurement, 74% of the eyes were within 0.25 D of target refraction and 97% were within 0.50 D. Mean absolute error at final measurement was 0.19 D, with 65% of the eyes achieving 20/20 vision. Customizable refractive results Dr. Brierley said in his summation that the adjustability of the Calhoun lens provides the opportunity to correct for residual spherical and cylindrical error after stabilization of the postoperative refraction. He also found he could minimize or eliminate error from capsular bag contraction, surgical wound healing and pre-existing astigmatism. He concluded that in patients with a history of laser refractive surgery, light-adjustable lens implantation and post-implantation adjustment provide a precise refractive outcome. He later added, this is customized surgery in its purest form. We can take a patient, even one who is not sure what he or she wants, and deliver precisely what is desired, and we can make that decision after surgery. And Bobby Qureshi, MD, FRCS, of London Eye Hospital had the following to say about implanting the Calhoun LAL in post-refractive patients: I have avoided lens power calculation challenges by implanting the Light Adjustable Lens in patients who have previously undergone LASIK, PRK and other corneal refractive surgery procedures. This lens gives me the ability to customize the refractive result after implantation by using a photopolymerization process that causes a precise change in the lens power. The Calhoun LAL offers flexibility One aspect of the Calhoun LAL Dr. Maloney emphasizes is the flexibility it gives to surgeons in achieving a variety of vision solutions that meet the needs and desires of individual patients. Other next-generation IOLs also in the pipeline The Calhoun LAL is not the only next-generation IOL in the investigational pipeline. Two other accommodating premium IOLs are in development. Lumina from Akkolens International (Breda, The Netherlands) is a dual-element accommodating lens implanted within the ciliary muscle with a 2.8-mm incision. The ciliary muscle drives the lens directly. Akkolens states that the Lumina can provide 4.00 D of accommodative power. The Lumina is now in 65 eyes in an ongoing clinical trial. The company recently reported that interim data has been excellent at near, intermediate and far distances. The company expects to apply for the CE mark in 2014.

5 Page 5 of 5 Fluid Vision from Power Vision (Belmont, Calif.), is an injectable IOL based on proprietary, fluidcontrolled technology. Clinical trials have shown this lens itself to be capable of delivering more than 5.00 D of true accommodation with excellent vision at all distances. The key to the wide range of accommodation the Fluid Vision provides is that the natural muscle movement of the eye moves the silicone fluid in the IOL to change the shape and thickness of the lens. The outer portion of the IOL that encases the fluid is made from a proprietary hydrophobic acrylic matched to the same refractive index as the fluid within. Though the most promising next-generation IOLs are still in the investigational pipeline, a more varied premium channel is expected to be available in the future. We are continuously improving the LAL and learning just how customizable it is, he says. The lens can correct astigmatism, spherical aberration, myopia and hyperopia. We can give patients monovision, enhanced depth of field, or even a reading add. With this lens, European cataract surgeons have already demonstrated they have the capability to meet the individual vision needs of their patients. OM REFERENCE 1. Brierley L. Refractive results after implantation of a light-adjustable intraocular lens in postrefractive-surgery cataract patients. Ophthalmology. 2013;120: Ophthamology Management, Volume: 18, Issue: March 2014, page(s): 50-52